+ All Categories
Home > Documents > Smoldering Multiple Myelomacme-utilities.com/mailshotcme/Material for Websites/COMy... ·...

Smoldering Multiple Myelomacme-utilities.com/mailshotcme/Material for Websites/COMy... ·...

Date post: 20-Mar-2019
Category:
Upload: hoangdang
View: 216 times
Download: 0 times
Share this document with a friend
34
Mayo Clinic College of Medicine Mayo Clinic Comprehensive Cancer Center Smoldering Multiple Myeloma S. Vincent Rajkumar Professor of Medicine Mayo Clinic Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida
Transcript

Mayo Clinic College of MedicineMayo Clinic Comprehensive Cancer Center

Smoldering Multiple Myeloma

S. Vincent RajkumarProfessor of Medicine

Mayo Clinic

Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida

Disclosures

No conflicts to disclose

Kyle RA et al. N Engl J Med 2007;356:2582-2590

SMM verus MGUS

• <10% BMPC AND • <3gm/dL M protein AND• No CRAB

• ≥10% BMPC OR• ≥3 gm/dL M protein AND• No CRAB

• Clonal PCPD• CRAB attributable

to the PCPD

CRAB= Hypercalcemia, renal failure, anemia, or lytic bone lesions attributable to a clonal plasma cell disorder

MGUS SMM MM

Rajkumar SV. Cecil Textbook of Medicine, 25th Edition, 2016

Previous Disease Definitions

No CRAB CRAB

Rajkumar SV. Cecil Textbook of Medicine, 25th Edition, 2015

Catch-22

Paradigm shift in diagnosis of myeloma

• <10% BMPC AND • <3 gm/dL M protein AND• No MDE

• ≥10%-60% BMPC OR• ≥3 gm/dL S. M protein OR• ≥500 mg/24h Ur. M protein AND• No MDE

• PCPD, AND• 1 or more MDE• CRAB• ≥60% BMPC• ≥100 FLC ratio• >1 MRI focal lesion

MDE, myeloma-defining events

MGUS SMM MM

Rajkumar SV, et al. Lancet Oncol. 2014;15(12):e538-e548.

Revised IMWG Criteria

Light Chain SMM

Kyle RA, et al. Lancet Haematol 2014;1:e28-36

Kyle R et al. N Engl J Med 2007;356:2582-2590

SMM verus MGUS

SMM Paradigm Shift

MGUS Myeloma

Exclude Multiple Myeloma

Low-dose Whole Body CT or PET-CT

Rajkumar SV, Dispenzieri A. In: Niederhuber JE, et al, eds. Abeloff’s Clinical Oncology, 5th Edition; 2013.Rajkumar SV. In: Goldman L and Schafer AI, eds. Goldman’s Cecil Medicine, 25th Edition. 2016.

Exclude Lytic Lesions

Bone Marrow Plasma Cell Estimation

Rajkumar SV et al. N Engl J Med 2011; N Engl J Med 2011; 365:474-475

• Regular (Wright’s, H & E)• Not immunostaining • Not flow

• Highest value

>100

<100

FLC Ratio >100 and Risk of progression to myeloma

Larsen J, et al. Leukemia advance online publication 27 November 2012; doi: 10.1038/leu.2012.296

Impact of renal failure

Gonsalves W. Blood Cancer J. 2015;5:e296.

Using the FLC ratio ≥100

• Measurable level of involved FLC: • ≥100 mg/L (≥10 mg/dL)

• Be wary of• Longstanding history• Minimal urine 24 hour M protein

• Assay

Rajkumar SV, Landgren O, Mateos MV. Blood 2015

Images courtesy of Jens Hillengass MD. University Hospital Heidelberg, S.D.G.;Hillengass J, Landgren O. Leuk Lymphoma 2013;54:1355–63.

MRI Focal Lesions

• 23/149 patients had >1 lesion; median TTP not patients with <= 1 FL and 13 months for those with >1 FL

Jens Hillengass et al. JCO 2010;28:1606-1610

MRI

• Definite focal lesions – at least 2• ≥5mm• Repeat in 3-6 months if in doubt

Rajkumar SV, Landgren O, Mateos MV. Blood 2015

Evolving MRI findings

Merz et al, Leukemia 2014

Diagnosis of Myeloma

• Judgment • Hypercalcemia• Renal Failure• Anemia• Bone

• Judgment • Interpreting FLC ratio• Clinical course• Imaging studies

Rajkumar SV, Dimopoulos M, Palumbo A, et al. Lancet Oncol. 2014;15(12):e538-e548.

©2012 MFMER | 3206302-23

Smoldering Multiple Myeloma

Low-risk SMM:

High-Risk SMM

MM

• >60% BMPC

• FLCr >100

• >1 MRI focal lesions

©2012 MFMER | 3206302-24

Smoldering Multiple Myeloma

Low-risk SMM: 5%/yr risk of MM

High-Risk SMM

25%/year risk of MM

High Risk SMM: Median TTP ~2 years

≥10% PCs plus:•SMM with M protein ≥3 gm/dL •Absence (<5%) of normal PCs by immunophenotyping plus Immunoparesis •Abnormal FLC ratio 8-100•Del(17p), t4;14, gain(1q21)•M protein ≥4 gm/dL•IgA SMM•Evolving pattern•Increased circulating plasma cells

Rajkumar SV, Landgren O, Mateos MV. Blood 2015

Copyright ©2008 American Society of Hematology. Copyright restrictions may apply.

Dispenzieri, A. et al. Blood 2008;111:785-789

FLC Ratio and risk of progression in SMM

Bianchi, et al. Leukemia advance online publication 18 September 2012; doi: 10.1038/leu.2012.237

High Circulating Plasma Cells and Risk of progression to myeloma

Follow up from diagnosis of smoldering multiple myeloma (years)

Per

cent

pro

gres

sing

PCLI <1

PCLI ≥1

Madan S. Mayo Clin Proc 2010

High Plasma Cell Proliferative Rate and Risk of progression to myeloma

Risk Cytogenetic Abnormalities % of patients

(N=351)

Median TTP to

Multiple Myeloma(months) a

Median TTP to Multiple

Myeloma or related

disorder(months) b

High-Risk t(4;14)Del(17p)Gain(1q21)*

13% 24 24

Intermediate-Risk

Trisomies 42% 34 34

Standard-Risk t(11;14), t(14;16), t(14;20), combined IgH translocations and trisomies†, and isolated monosomy 13

30% 55 54

Low-Risk No abnormalities detected on FISH‡ 15% Not reached

101

Rajkumar SV et al Leukemia. 2013 Aug;27(8):1738-44; Neben et al. J Clin Oncol 2013

Cytogenetic Abnormalities and risk of progression in SMM

FISH Abnormalities

High risk: any of del(17p13), t(4;14), or 1q21

Neben et al, JCO 2013

Risk factor Progression within 2 years eMP only 64%eHb only 65%Both eMP and eHb 82%eMP, eHb, and BMPC ≥20% 91%

eMP: 10% increase in M protein within 6 months (if M-protein ≥3 g/dl) or ≥25% increase in M protein within 12 months (minimum 0.5 g/dl)

Evolving M protein Levels

Ravi P, et al. Blood Cancer J 2016;6:e454-

eHb: ≥0.5 g/dL decrease within 12 months

Fernández de Larrea C, et al. Leukemia 2018 (ePub)

Management of SMM

When Should Treatment Be Initiated?

Potential New Myeloma or Smoldering Myeloma

Observation

Rajkumar SV, Landgren O, Mateos MV. Blood 2015

Any Myeloma Defining Events?• CRAB, • >60% PC, • FLC >100, • MRI >1 focal

No Myeloma Defining Events (SMM)

Treat as Myeloma

High Risk SMM(Median TTP ~2 years)

Low Risk SMM(~5% per year PD)

To Treat or Not to Treat?

Especially Evolving, or Many high risk

factors


Recommended