Mayo Clinic Myeloma Amyloidosis Dysproteinemia Group

Mayo Clinic College of Medicine

Mayo Clinic Comprehensive Cancer Center

Mayo Clinic Myeloma Amyloidosis Dysproteinemia Group

Scottsdale Arizona Rochester Minnesota Jacksonville Florida

Vision Statement

To Advance Individualized Care Have a

Global Impact and Cure

Myeloma and Related Disorders

copy2014 MFMER | 3357202-3

Strength of Our Practice Mayo Clinic 1960-2014

Strengths

bull Largest Myeloma and Related Disorders Groups in the World

bull Multidisciplinary Group

bull Hematologists

bull 20 at Mayo Clinic Rochester MN

bull 6 at Mayo Clinic Arizona

bull 4 at Mayo Clinic Florida

bull 14 hematologists are at Professor Level

bull Specialists in Divisions other than HemOnc

bull 7 across the 3 sites

bull Complete Integration across the 3 Mayo Clinic sites

bull Myeloma SPORE (PI Leif Bergsagel)

Strengths

bull International Leadership in research education and practice

bull Molecular Classification of MGUS SMM and Myeloma

bull Risk-adapted therapy of Myeloma and Related Disorders

bull Epidemiology of Plasma Cell Disorders

bull Related Plasma Cell Disorders

bull MGRS

bull Amyloidosis

bull POEMS

bull Castlemanrsquos disease

bull WM

bull Mayo Led Clinical Trials

bull Leadership in ECOG

bull Extensive Clinical and Laboratory Databases

Unique Programs

bull Epidemiology Biomarkers (Rajkumar Kyle Kumar Dispenzieri)

bull Virotherapy (Russell Dingli Peng)

bull Center for Individualized Medicine (Stewart)

bull Vaccine and Adoptive Cell Therapy (Lin)

bull Novel Imaging for Myeloma (Drake)

bull Novel Laboratory Evaluation (Ketterling Morice)

bull Mass Spec (Murray Bergen Barnidge Kurtin)

bull Genomics (Stewart Bergsagel Fonseca)

bull Novel Therapeutics (Stewart Bergsagel Kumar)

bull Immunotherapy (Lin Chanan-Khan)

bull Hematology-Oncology Outcomes Research-Oriented Group (Go Hashmi)

International Leadership

bull NCI Multiple Myeloma Steering Committee

bull Shaji Kumar Chair Vincent Rajkumar- member

bull ECOG Myeloma Committee

bull Vincent Rajkumar Chair

bull Journals (Editors of Myeloma Section)- Leukemia European Journal of Haematology American Journal of Hematology Blood Cancer Journal Mayo Clin Proc Clin Lymphoma and Myeloma Amyloid


bull International Myeloma Working Group (IMWG)

bull Vincent Rajkumar co-chair

bull International Myeloma Foundation (IMF)

bull Robert Kyle and Vincent Rajkumar Board Members Robert Kyle Chair of the Scientific Advisory Board

bull International Waldenstroumlms Macroglobulinemia Foundation (IWMF)

bull Robert Kyle and Steve Ansell Board of Trustees Robert Kyle chair Scientific Advisory Committee

bull International Society of Amyloidosis (ISA)

bull Angela Dispenzieri President

bull International Myeloma Society (IMS)

bull Angela Dispenzieri Treasurer

bull International Kidney and Monoclonal Gammopathy Research Group (IKMG)

bull Nelson Leung President Angela Dispenzieri Treasurer

Clinical Trial Leadership

bull Principal Investigator (PI) Role on many prominent NationalInternational Phase III Trials

bull Pomalidomide trials (Martha Lacy)

bull E1A06 MPT vs MPR (Keith Stewart)

bull MM 020 Rd vs MPT (Angela Dispenzieri)

bull S0777 Rd vs VRd (Angela Dispenzieri)

bull ASPIRE Rd vs KRd (Keith Stewart)

bull E1A11 VRD vs KRd (Shaji Kumar)

bull Ixazomib Rd vs IRd (Vincent Rajkumar)

bull Ixazomib Phase III AL (Angela Dispenzieri)

bull S1304 Highstd dose carfilzomib (Sikander Ailawadhi)

bull S1211 RVd vs RVd-Elo (Sikander Ailawadhi)

Publications

bull ~80-100 per year excluding abstracts and book chapters

Education

bull httpwwwmsmartorg Practice Guidelines

bull wwwtwittercommayomyeloma

bull Myeloma Fellowship

bull Kurtz Myeloma Research Fellowship

bull Myeloma Book - Fully Mayo authored (Springer 2013)

bull Amyloidosis Book (Springer 2010)

bull UpToDate (All chapters related to myeloma and related disorders)

bull Wintrobe Clinical Hematology

MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs

Observation only Observation only Therapy required

Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells

MDEs Hypercalcemia anemia renal failure or lytic bone lesions attributable to plasma cell disorder

gt=60 clonal PCs gt=100 FLC ratio gt1 focal lesion on MRI

Kyle RA N Engl J Med June 21 2007 Rajkumar SV Lancet Oncology 2014

Developed Definition and Classification of MGUS SMM MM

Kyle R et al N Engl J Med 20063541362-1369

Determined the Prevalence of MGUS in USA

Kyle RA et al N Engl J Med 2006 Volume 3541362-1369

bull MGUS present in 3 of general population gt50 years

bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women

Dispenzieri A et al Lancet 2010 3751721 - 1728

Defined and Determined Prevalence of Light Chain MGUS

bull LC-MGUS is present in 08 of general population gt50 years

LC-MGUS LC-MGUS

Landgren OhellipRajkumar SV Leukemia 2014

n-=12482

Blacks

Whites

Hispanics

Determined 2-fold Increased Prevalence of MGUS among African Americans in USA


Defined Risk of Progression of MGUS and SMM


Estimated MGUS Annual Health Care Costs in USA

Go RS et al Leukemia 2016 In Press

bull About 540000 individuals living with a diagnosis of MGUS

bull At least $110 million annual cost to health care

Copyright copy2009 American Society of Hematology Copyright restrictions may apply

Landgren OhelliphellipRajkumar SV Blood 20091135412-5417

Demonstrated MGUS always precedes MM

100 had

preceding

MGUS

Developed Cytogenetic Classification of SMM

Del 17p t(414) Gain(1q)

No

cytogenetic abnormalities

All other

High-Risk Low-Intermediate Low-Risk

Rajkumar SV Leukemia 2013271738-1744 Neben et al J Clin Oncol 2013

Trisomies

High-Intermediate

Median TTP ~2 years Median TTP ~3 years Median TTP ~5 years Median TTP ~10 years

Myeloma Biology

Led Many Studies on Pathogenesis of MGUS and its progression to myeloma

Bergsagel PL et al Proc Natl Acad Sci U S A 19969313931-6 Bergsagel PL et al Blood 2005106296-303 Fonseca R et al Blood 20021001417-24 Fonseca R et al Cancer Res 2004641546-58 Rajkumar S V Clin Cancer Res 2009155606-5608

copy2009 by American Association for Cancer Research

First determined two major subtypes of Myeloma Hyperdiploid and Non-Hyperdiploid

Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression

Fonseca Blood 10225622003

Developed genetic classification of hyperdiploid myeloma

Chng W J et al et al (2007) Cancer Research 67(7) 2982ndash2989

First to show inverse relationship between IgH Translocations and trisomies

Fonseca R et al (2003) Blood 102(7) 2562ndash2567

First comprehensive genetic description of MGUS and AL MGUS similar to MM and AL 50 t(1114)

Hayman S R et al Blood 98(7) 2266ndash2268

Fonseca R et al Blood 100(4) 1417ndash1424

Developed VkMYC mouse model of Myeloma

Chesi et al Cancer Cell 2008

28

Affer et al Leukemia 2014

Method MYC

rearrangements

FISH 15

aCGH 44

Either 49

13 Ig enhancers - distributed equally across genetic subtypes

23 non-Ig enhancers - more common in hyperdiploid

Juxtaposition of super enhancers adjacent to MYC

Identified MYC rearrangements in ~50 of MM patients

Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66

Identified that mutations of NFkB are frequent in Myeloma

Keats Cancer Cell 2008

Described Clonal Tides in Myeloma

Keats J J et al Blood 20121201067-1076

copy2012 by American Society of Hematology

Myeloma Clinical Studies

Healthcare Disparities in Myeloma

bull First to show that Hispanics have the worst outcome of all racialethnic subgroups in myeloma

bull First to explore the benefit of NCINCCN centers on outcomes in myeloma

bull Benefit of NCI centers within SEER registry seen only in Whites

bull Benefit of NCCN centers within SEER registry seen in Whites and African-Americans not in other minorities

Ailawadhi S et al Br J Haematol 2012158(1)91-8

Ailawadhi S et al Cancer 2016 122(4) 618-25

1961-70

1971-80

1981-90

1991-2000

2001-2010

Kumar S Blood 2008111 2516 ndash 2520 Kumar S Leukemia (2014) 28 1122ndash1128

Demonstrated Improved Survival in Myeloma

Led Development of New Diagnostic Criteria for Myeloma

Rajkumar SV Lancet Oncology 2014

Led Development of International Staging System for Myeloma

Greipp PR J Clin Oncol 2005233412-3420

Stage Survival in Months

Developed Cytogenetic Classification of Myeloma

t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies

t(414) (FGFR3 MMSET)

~10 have both trisomies and IgH translocations

Fonseca R et al Leukemia 2009232210-21 Kumar S et al Blood 20121192100-5

Developed Cytogenetic Myeloma Risk-Stratification

t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)

High-Risk Intermediate-Risk Standard-Risk

msmartorg

Presence of trisomies ameliorates high risk

Median survival lt3 years Median survival 6-7 years

Trisomies

Gain (1q)


Durie et al Leukemia 2006201467-73

Leadership Role in Development of IMWG Response Criteria for Myeloma

Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13

All others including

t(1114)

Poor 247 mos

Intermediate 423 mos

Good 510 mos

Fonseca et al Blood 1014569 2003

First Developed Global Genetic Prognostic Model for

Myeloma

Demonstrated that Clinical Activity of a New Myeloma Drug can be

predicted by drug response in de novo VkMYC mice

Updated from Chesi et al Blood 2012

Response rate gt20

as a single agent in

patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein

Pioneered out patient transplant for myeloma with lowest complication rate reported

Gertz et al Mayo Clin Proc 2008 Oct83(10)1131-8

Development of New Drugs in Multiple Myeloma

Led first phase III

of isatuximab

First published phase II of dinaciclib

Led pivotal trial that led

to full approval of carfilzomib

First published phase II of ixazomib

First published phase II of pomalidomide

2011-2015 2016-

Co-investigator in

Summit Trial that led to approval of bortezomib

Led trials that led to approval of thalidomide

First published phase II of lenalidomide

1999-2010

Best Response within 4 Cycles using ECOG criteria

198 of 202 eligible pts

bull ThalDex 63

bull Dex 41

1-sided

p-value=0002

Rajkumar et al J Clin Oncol 200624431-436

Led trial that led to approval of thalidomide in myeloma ECOGCTSU Randomized Phase III Trial (E1A00)

Number at risk RD 223 179 103 37 0 Rd 221 192 103 37 0

00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24

Treatment ON 1 year OS rate RD 35223 87 Rd 10222 96

Rajkumar SV et al Lancet Oncology 2009

Led trial that showed low-dose Dex improves survival

Established the Rd regimen that is now backbone for many myeloma regimens

Copyright copy American Society of Clinical Oncology

Lacy M Q et al J Clin Oncol 275008-5014 2009

Led first published phase II of Pomalidomide in Myeloma

Progression-free Survival

Stewart AK et al N Engl J Med 2015372142-152

Led trial that led to full approval of carfilzomib in myeloma KRd vs Rd Aspire Trial

Figure Response with increasing duration of therapy (A) and waterfall plot of best M-protein response (B) among 52

response-evaluable patients treated at the recommended phase 2 dose One patient in phase 2 was excluded from the

response-evaluable populati

Kumar et al The Lancet Oncology Volume 15 Issue 13 2014 1503 - 1512

Led first published phase II of ixazomib in Myeloma

First phase 1 trial of Venetoclax in Myeloma Demonstration of single agent activity

Kumar S et al ASH 2015

First described association of myeloma with reversible pulmonary hypertension

eastern cooperative oncology group

Leading Current National Trial for Newly Diagnosed Myeloma

Actively Accruing

E4A03 Phase III ndash Newly Diagnosed Myeloma PI Shaji Kumar

VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy

till prog or toxicity

Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS

Vrana JA Gamez JD Madden BJ Theis JD Bergen HR 3rd Dogan A Blood 2009114(24)4957-4959

Developed Classification of amyloidosis by laser microdissection and mass spectrometry based

proteomic analysis in clinical biopsy specimens

Developed Amyloid Proteome Signature

Vrana JA et al Clinical diagnosis and typing of systemic amyloidosis in subcutaneous

fat aspirates by mass spectrometry-based proteomics Haematologica 201499(7)1239-1247

Troponin T TnT lt0035 mcgL

NT-proBNP lt332 ngL

Troponin I TnI lt01 mcgL

NT-proBNP lt332 ngL

Developed Staging for AL amyloidosis

Mayo AL Staging v20

Dispenzieri et al Journal of Clinical Oncology 20041223751-7

Developed Staging System for AL Amyloidosis

Mayo AL Staging v 30 (n=758)

Kumar S et al Journal of Clinical Oncology 201230989-995

Risk factors 1 point each for

score 0-3 Stage 1-4

bull FLC-diff ge 180 mgL

bull cTnT ge 0025 mcgL

bull NT-ProBNP ge1800 ngL

No at risk 1247 601 352 202 95 30 7

N Median OS

AL-only (le 10 BMPC) 679 42 m

AL-PCMM (gt 10 BMPC) 476 16 m

AL-CRAB 100 11 m

Developed definition of MM in patients with AL Amyloidosis

Overall survival in patients with gt10 BMPC similar to patients with end-organ damage (CRAB)

P lt0001

Follow up from diagnosis months

Kourelis et al JCO 201331(34)4319-4324

First published study of CyBorD in AL Amyloidosis The current standard frontline treatment

Defined Role of transplantation in AL amyloidosis

Developed Transplant Eligibility Criteria for AL Amyloidosis

10 month mortality 25 P=00003

Troponin T lt006 mcgL

Troponin T ge006 mcgL

NT-proBNP lt5000 pgL

NT-proBNP ge 5000 pgL

100 day mortality 25 Plt00001

Gertz et al Bone Marrow Transplantation 201348(4)557-61

Pioneered Treatment of AL Amyloidosis with Sequential Heart and Stem Cell Transplantation

Lacy MQ Dispenzieri A Hayman SR et al The Journal of heart and lung transplantation

the official publication of the International Society for Heart Transplantation 200827(8)823-829

Leung N Griffin MD Dispenzieri A et al American journal of transplantation 20055(7)1660-1670

Pioneered treatment of AL Amyloidosis with Sequential Kidney and Stem Cell Transplantation

Developed Len-Dex in AL Amyloidosis

Dispenzieri et al Blood 2007 Jan 15109(2)465-70

Developed CRD for AL Amyloidosis

Kumar SK Hayman SR Buadi FK et al Blood 2012119(21)4860-4867

Developed Pomalidomide-Dex for AL Amyloidosis

Dispenzieri A Buadi F Laumann K et al Blood 2012119(23)5397-5404

Led first antibody trial for AL amyloidosis

Developed Response Criteria for AL amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g

CR (97 patients 36 deaths100 py)

VGPR (233 patients 96 deaths100 py)

PR (140 patients 237 deaths100 py)

NR (179 patients 472 deaths100 py)

p=001

plt0001

plt0001

Survival of 649 patients based

on hematologic response at 6 months

Led validation of response criteria for AL

amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g

NT-proBNP progression (at least 300 ngL and 30 increase) 169 patients

NT-proBNP stable 108 patients

NT-proBNP response (at least 300 ngL and 30 decrease) 100 patients

plt0001

plt0001

Survival of 377 patients with

baseline NT-proBNP ge650 ngL according

to NT-proBNP response and progression

at 6 months

Palladini G Dispenzieri et al Journal of clinical oncology 2012 30 4541-9

Largest US experience with familial amyloidosis

POEMS SYNDROME

Major Contributions in Patients with POEMS Syndrome

1 Largest single institution series mdash presentationoutcomes

2 Diagnosis

bull Unique bone marrow findings

bull Platelet count to differentiate from CIDP

bull VEGF to differentiate POEMS from other diseases

3 Treatment

bull Expectations with radiation therapy

bull Expectations with ASCT

bull First report of lenalidomide

bull First report of cyclophosphamide-bortezomib-dex

4 Prognosis

bull High platelets risk for stroke

bull Low albumin risk for relapse

Demonstrated that Overall Survival in POEMS Syndrome Better than Previously Reported

Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years

Dispenzieri A Kyle RA Lacy MQ et al Blood 2003101(7)2496-2506

Demonstrated unique BM Findings in POEMS lymphoid aggregates rimmed by PC amp

megakaryocyte atypia

Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC

Defined Role of Primary Radiation therapy for POEMS Syndrome (n=38)

bull 4 year OS 97

bull 4 year failure free survival 52

bull Risk factors for failure bull DLCOlt70

bull Elevated urine protein

Failure defined as receiving a new treatment

Median follow-up 43 months

Humeniuk Blood 2013122(1)68-73

Demonstrated Role of Stem Cell Transplant for POEMS

00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al

Between 31999-102011 59 patients had ASCT

Median follow-up of 40 months (0-147 months)

OS

PFS

DSouza A et al Blood Jul 5 2012120(1)56-62

Demonstrated Improvement in Peripheral Neuropathy with ASCT in POEMS

Karam C Klein CJ Dispenzieri A et al Neurology 201584(19)1981-1987

Waldenstrom Macroglobulinemia (WM)

Chng W J et al Blood 20061082755-2763

First genetic and genomic studies in WM Lack of IgH translocations and 6q deletions in 50

Described flare of Waldenstrom after Rituximab

Largest US experience with CAD

Rare Plasma Cell Disorders

1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100

Clinical and Genetic Description of Plasma Cell Leukemia

MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs

FISH (MGUS n=184 SMM n=116 relapsed MM n=62 and PCL n=26)

aCGH (newly diagnosed MM n=224 relapsed MM n=158 and HMCLs n=48)

p 53 mutational status was evaluated in relapsed MM (n=84) and HMCLs (n=48)

Tiedemann et al Leukemia 2008 22 1044-1052

Studied 8 patients with 17p deletions at RR 7 did not have deletion at diagnosis

First published report of stem cell transplant for TEMPI syndrome

First to publish stem cell transplat for scleromyexedema

Vision Statement

To Advance Individualized Care Have a

Global Impact and Cure

Myeloma and Related Disorders

copy2014 MFMER | 3357202-3


Strengths



bull Hematologists









Strengths






bull MGRS

bull Amyloidosis

bull POEMS


bull WM




Unique Programs











































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








copy2014 MFMER | 3357202-3


Strengths



bull Hematologists









Strengths






bull MGRS

bull Amyloidosis

bull POEMS


bull WM




Unique Programs











































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Strengths



bull Hematologists









Strengths






bull MGRS

bull Amyloidosis

bull POEMS


bull WM




Unique Programs











































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Strengths






bull MGRS

bull Amyloidosis

bull POEMS


bull WM




Unique Programs











































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Unique Programs











































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs







































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs

































Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs




















Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Publications


Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Education









MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








MGUS and SMM

MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








MGUS SMM MM

Asymptomatic

No end-organ damage

Asymptomatic

No MDEs

MDEs


Clinical

Picture

Therapy

Bone

Marrow M

Protein

lt10 plasma cells

AND lt3gmdL M

protein

10-60 plasma

cells OR ge3 gmdL

M protein

ge10 plasma

cells









bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs












bull 17 in 50-59

bull gt5 in over 70

bull Men gt Women




LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











LC-MGUS LC-MGUS


n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









n-=12482

Blacks

Whites

Hispanics












100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs


















100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs
















100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











100 had

preceding

MGUS



No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










No


All other



Trisomies

High-Intermediate


Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Myeloma Biology





Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs












Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









Gene expression

Primary

IgH

TRXs

Non

Hyperdiploid

No

IgH

TRX

Hyperdiploid

Secondary

IgH

TRX

Ploidy

variable

Gene expression











28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs

















28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs















28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs













28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








28


Method MYC

rearrangements

FISH 15

aCGH 44

Either 49





Condition MYC

rearrangements

Untreated 47

Relapsed 52

t(1114) 25

Hyperdiploid 66














1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs





















1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs



















1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs
















1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs















1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








1961-70

1971-80

1981-90

1991-2000

2001-2010









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs














t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs












t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









t(1416) (C-MAF)

t(1420) (MAF-B)

t(1114) (CCND1)

t(614) (CCND3)

Trisomies





t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









t(1416) t(1420) Del 17p

t(1114)

t(614)

t(414)


msmartorg



Trisomies

Gain (1q)




Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








Su

rviv

al

pro

bab

ilit

y

Months

Plt0001

t(414)

t(1416)

-17p13

D13


t(1114)

Poor 247 mos


Good 510 mos



Myeloma




Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











Response rate gt20


patients

Response rate lt20


patients

Response is gt50

reduction in

paraprotein




Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









Led first phase III

of isatuximab






2011-2015 2016-

Co-investigator in




1999-2010



bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










bull ThalDex 63

bull Dex 41

1-sided

p-value=0002




00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









00

02

04

06

08

10

0 6 12 18 24

Surv

ival pro

bab

ility

Months

0

02

04

06

08

1

0 6 12 18 24





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs
























Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs





















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs


















Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs













Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










Actively Accruing


VRd x 12

cycles

KRd x 12

cycles

Revlimid

X 2years

Revlimid

Until prog

Continue therapy


Continue therapy


R

A

N

D

O

M

I

Z

A

T

I

O

N

AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








AMYLOIDOSIS








NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs















NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs












NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









NT-proBNP lt332 ngL


NT-proBNP lt332 ngL


Mayo AL Staging v20






score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs












score 0-3 Stage 1-4




No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








No at risk 1247 601 352 202 95 30 7

N Median OS



AL-CRAB 100 11 m



P lt0001


























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs































0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs






























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs





























0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs





















0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs


















0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs
















0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs














0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs












0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

po

rtio

n s

urv

ivin

g





p=001

plt0001

plt0001




amyloidosis

0 12 24 36 48

Time (months)

00

01

02

03

04

05

06

07

08

09

10

Pro

port

ion s

urv

ivin

g




plt0001

plt0001




at 6 months



POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








POEMS SYNDROME



2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










2 Diagnosis




3 Treatment





4 Prognosis




Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









Overa

ll s

urv

iva

l (

)

Months

0

20

40

60

80

100

0 50 100 150 200 250 300 350

Median 138 years




Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










Dao et al Blood 2011 117(24)6438-44

HampE 200x CD138

l k

33 of 67 cases

had lymphoid

aggregates

32 of these had

clonal PC

5967 had mega

rimming or clonal

PC


bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









bull 4 year OS 97








00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









00

02

04

06

08

10

0 12 24 36 48 60 72 84 96

Months post-ASCT

Perc

en

t su

rviv

al



OS

PFS










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs
















1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs














1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs













1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs










1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs









1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs








1 4 820 18

33

83 92

0

10

20

30

40

50

60

70

80

90

100


MGUS

SMM

newly diagnosed MM

first relapse MM

second relapse MM

PCL

HMCLs











Date post:	16-Oct-2021
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