February 1-2, 2019 Vienna, Austria · 19 European Multiple Myeloma Academy | February 1-2, 2019 |...

1 19th European Multiple Myeloma Academy | February 1-2, 2019 | Vienna, Austria

February 1-2, 2019Vienna, Austria

Chairs:Heinz Ludwig (Austria)Jesús San-Miguel (Spain)

3 19th European Multiple Myeloma Academy | February 1-2, 2019 | Vienna, Austria19th European Multiple Myeloma Academy | February 1-2, 2019 | Vienna, Austria 2

CONTACTS

Scientific Coordinator:

Univ.-Prof. Dr. Heinz LudwigWilhelminen Cancer Research Institutec/o Dept. of Medicine I, Centre of Oncology,Haematology and Palliative CareWilhelminenspital, Montleartstr. 371160 Vienna, Austria+43 1 491 50 21 [email protected]

and

EMERI – Medical Education and Research [email protected]

Congress & Travel Management:

Mondial Medica Reisebuero GmbHWaehringer Guertel 18-20 (AKH)1090 Vienna, Austria+43 1 402 40 61-0www.emma-vienna.org

Verena [email protected]. (FH) Barbara [email protected]

19th European Multiple Myeloma Academy


InterContinental Hotel Vienna

Chairs:Heinz Ludwig (Austria)Jesús San-Miguel (Spain)



WELCOME

WELCOME .............................................................................5

PROGRAMMEThursday, January 31 – Dinner Meeting .......................... 7Friday, February 1 – Morning Session ............................. 7Friday, February 1 – Afternoon Session .......................... 8Saturday, February 2 – Morning Session ........................ 9

FACULTY-BIOGRAPHIES & KEYPOINTSJoan Bladé ...................................................................... 11Mario Boccadoro ............................................................14Michele Cavo ..................................................................16Mark Cook ..................................................................... 18Hermann Einsele ............................................................20Francesca Gay ...............................................................22Dirk Hose ........................................................................24Alessandra Larocca ........................................................26Heinz Ludwig ...................................................................28Maria-Victoria Mateos ......................................................30Giampaolo Merlini ...........................................................32Philippe Moreau ..............................................................34Mohamad Mothy .............................................................36Enrique Ocio ...................................................................38Bruno Paiva ....................................................................40Charlotte Pawlyn ............................................................42Leo Rasche ....................................................................44Jesús San-Miguel ...........................................................46Pieter Sonneveld ............................................................48Evangelos Terpos ...........................................................50Niels Van de Donk ...........................................................52Elena Zamagni ................................................................54

CONTENTS

Welcome to the 19th European Multiple Myeloma Academy Meeting in Vienna. We are delighted that you decided to participate in this exciting event.

The recent years showed remarkable progress in our understanding of the bio-logy of multiple myeloma and related diseases. It led to the introduction of novel therapies that increase our options of controlling this still difficult to treat disease. During this EMMA meeting, we will discuss new insights into the stepwise process leading to the evolvement of the disease, the role of genetic testing, NGS and the impact of the microenvironment on myeloma growth.

An important part of the meeting will be devoted to practical issues of manage-ment of patients with multiple myeloma and related diseases. This will include workshops, formal presentations and discussion rounds with special emphasis on new data from recent clinical studies as well as their relevance for inclusion in present treatment paradigms and in every day clinical practice.

We aim to create a friendly, collegial atmosphere and like to encourage you to interact with the faculty and other delegates to find answers to difficult questions that are important for optimal patient care in your daily clinical practice.

Heinz Ludwig and Jesús San-MiguelChairmen of the meeting

Dear Colleagues,


PROGRAMME PROGRAMMEThursday, January 31

19:30 – 20:45 Dinner Buffet Meeting (limited access, registration required) When should treatment be started at relapse and how to follow patients during remission and therapy? Joan Bladé

Friday, February 1 – Morning Session

08:15 – 08:20 Welcome Heinz Ludwig and Jesús San-Miguel

08:20 – 08:45 From MGUS to multiple myeloma: Insights into the pathophysiology Dirk Hose

08:45 – 09:10 The role of bone marrow stroma in multiple myeloma Charlotte Pawlyn

09:10 – 09:35 NGS in MM, clinical relevance and prospects for the future Leo Rasche

09:35 – 10:05 Expert discussion: Bringing the evolving wealth of information into clinical perspective Moderator: Heinz Ludwig Participants: Dirk Hose, Charlotte Pawlyn, Leo Rasche • What induces progression? • What is different between transient MGUS and permanent MGUS? • Which genomic changes indicate progression to MM? • Are changes in BM environment during transformation from MGUS to MM the cause or the consequence of transformation? • Will NGS improve selection of individualized therapy in MM? • Questions from the audience

10:05 – 10:35 Coffee Break

10:35 – 11:00 NGF for immune profiling, MRD assessment and detection of circulating plasma cells Bruno Paiva

11:00 – 11:25 Diagnostic workup in patients with paraproteinemia Francesca Gay

11:25 – 12:15 Workshops • Renal disease in multiple myeloma: Pathophysiology and treatment Mark Cook • Pathophysiology and Management of myeloma bone disease Evangelos Terpos • How I treat extramedullary myeloma and plasma cell leukemia Joan Bladé

12:15 – 13:15 Lunch Buffet


PROGRAMMEFriday, February 1 – Afternoon Session

13:15 – 13:40 Imaging in myeloma bone disease Elena Zamagni

13:40 – 14:05 Risk stratification of smoldering myeloma and recommendations for management María-Victoria Mateos

14:05 – 14:30 Optimizing induction and consolidation therapy in TE patients Philippe Moreau

14:30 – 14:55 Strategies for optimizing maintenance treatment Michele Cavo

14:55 – 15:25 Expert discussion: best approaches in early MM and TE patients Moderator: Philippe Moreau Participants: Michele Cavo, María-Victoria Mateos, Charlotte Pawlyn • What are the best markers for progression of SMM? • What is the optimal number of cycles for induction and consolidation? • Is there any sense in switching to another protocol if patients do not respond to the first line TX? • Who benefits from consolidation?

• What is the optimal maintenance therapy for HR-disease?

• Questions from the audience

15:25 – 15:55 Coffee Break

15:55 – 16:45 Workshops (programme repeated)

16:45 – 17:10 Treatment options for elderly fit patients Mario Boccadoro

17:10 – 17:35 Management of elderly, unfit and frail patients Alessandra Larocca

17:35 – 18:05 Expert discussion: Management of elderly patients Moderator: Heinz Ludwig Participants: Mario Boccadoro, Alessandra Larocca, Evangelos Terpos • How to improve induction therapy? • Optimal approach in high-risk patients? • Is maintenance therapy a valuable option for elderly patients? • Strategies for patients not responding to induction? • Questions from the audience

19:00 Delegate Dinner

PROGRAMMESaturday, February 2 – Morning Session

07:45 – 08:15 Breakfast Meeting (limited access, registration required) Transplantation and cellular therapies in MM Mohamad Mohty

08:30 – 09:00 Keynote lecture: The roadmap to cure patients with multiple myeloma? Jesús San-Miguel

09:00 – 09:25 Impact of monoclonal and bispecific antibodies in myeloma therapy today and tomorrow Niels van de Donk

09:25 – 09:50 How I treat high risk disease Pieter Sonneveld

09:50 – 10:20 Panel discussion: How to cure more patients with myeloma? Moderator: Jesús San-Miguel Participants: Pieter Sonneveld, Hermann Einsele, Niels van de Donk • Risk adapted therapy or ‚optimal‘ treatment for all? • Can we overcome the negative impact of HR disease with presently available approaches? • Is there any guidance for stopping therapy in patients with prolonged MRDneg? • Should early treatment be recommended in case of change from MRDneg to MRDpos

• The best approach in HR disease • Questions from the audience

10:20 – 10:50 Coffee break

10:50 – 11:15 Sequencing in relapsed/refractory disease Heinz Ludwig

11:15 – 11:35 Innovative drugs for myeloma therapy Enrique Ocio

11:35 – 12:00 Strategies for optimizing CAR-T cell and other cellular therapies Hermann Einsele

12:00 – 12:30 Panel discussion: How to optimize treatment of relapsed or refractory disease? Moderator: Jesús San-Miguel Participants: Enrique Ocio, Hermann Einsele, Heinz Ludwig • Are there golden rules for relapse therapy? • Options after failure of anti-CD38 therapy • What are the prospects of new, still experimental drugs and strategies? • What to do if all new approved therapies fail? • Questions from the audience

12:30 – 12:55 New developments in amyloidosis Giampaolo Merlini

12:55 – 13:00 Closure of the meeting

from 13:00 Lunch Buffet


FACULTY BIOGRAPHIES & KEYPOINTS

Joan Bladé, MD, PhD, was born in Benissa-net, Catalonia, Spain. He graduated from the University of Barcelona in 1976, and comple-ted his fellowship at the Hospital Clínic of Bar-celona (1976–1980), where he is now a Senior Consultant.

Dr. Bladé did his PhD on prognostic factors in multiple myeloma. Since 1981 he has been devoted to the care of patients with multiple myeloma and his research is focused on cli-nical aspects, prognosis, and treatment of this disease. In 1992, he was a visiting clini-cian for a year in the Dysproteinemia Clinic at the Mayo Clinic. He was Executive Secretary of the Spanish cooperative PETHEMA group from 1994 to 2001, and has also been Chair-man of PETHEMA myeloma trials since 1985.

Dr. Bladé has been a member of the Scientific Advisory Board of the International Myeloma Foundation (IMF) since 1997. He is also the Secretary of the International Myeloma Socie-ty (IMS). He has conducted a number of trials published in high-impact journals. He has pu-blished around 280 articles in peer-reviewed journals and 40 book chapters, mainly on mul-tiple myeloma and monoclonal gammopathy of undetermined significance (MGUS). In 2010, Dr. Bladé received the Robert A. Kyle Lifetime Achievement Award, and in 2012, he received the Joseph Michaelli Award for Contributions to Myeloma Research.

JOAN BLADÉ

University Hospital Clinic of BarcelonaBarcelona, Spain


When should treatment be started at relapse and how to follow patients during remission and therapy? Dinner Buffet Meeting: Thursday, January 31, 19:30 – 20:45

JOAN BLADÉ

1. Most patients at relapse have similar clinical presentation than at diagnosis, particularly in terms of renal failure, urine M-protein excre-tion, hypercalcemia or plasmacytomas.

2. Half of the patients develop asymptomatic relapse/progression.

3. Patients relapsing from CR have a bet-ter outcome than those progressing from VGPR or PR.

4. Patients with 24-hour urine protein excretion > 200mg have poorer outcome. No patient without light chain protein excretion al dia-gnosis (urine IF negative) relapse only with light chain in the urine.

5. The median time to require therapy in pati-ents with asymptomatic relapse/progression is 6 months.

6. One fourth of patients with asymptomatic relapse/progression do not require therapy within the first two years from relapse. The patients have an excellent outcome with a median survival from relapse longer that 8 years.

7. Patients should be treated at symptomatic relapse or at significant paraproteinemic progression.

8. Indications for early treatment at asympto-matic paraproteinemic relapse are: previous aggressive clinical presentation, increasing free light chains in the urine (> 500 mg/24-hours), evident decrease in Hb level, ult-ra-high risk myeloma, EMD or PCL at pre-sentation.

9. Bone aspirate or imaging techniques during follow-up should be performed only when clinically indicated (i.e., unexplained cytope-nias, suspicion of bone or EMD).

10. The presence of oligoclonal bands in pati-ents in CR, frequent after SCT or treatment with proteasome inhibitors or IMiDs, should be recognized.

How I treat extramedullary myeloma and plasma cell leukemiaWorkshop: Friday, February 1, 11:25 – 12:15 and 15:55 – 16:45

JOAN BLADÉ

1. Plasmacytomas in MM can consist of local growth (paraskeletal - PS -) or hematogenous spread (extramedullary disease - EMD -).

2. EMD consists on single or multiple nodules in skin, liver, breast, kidney, lymph nodes or in leptomeningeal (CNS) involvement.

3. At diagnosis the most frequent location of EMD is the skin while at relapse liver, pleura and CNS are more frequently involved.

4. The frequency of EMD at diagnosis of MM is between 1.7 to 4.5% while at relapse it ran-ges between 3.4 to 10%.

5. The frequency of solitary plasmacytomas is similar at diagnosis and at relapse ranging between 6 and 34%, depending on the series.

6. PET/CT is the most useful imaging technique in the search of plasmacytomas. However, MRI is more useful in assessing in case of spinal cord compression or CNS involvement.

7. Patients with EMD have a greater incidence if high-risk features and poorer prognosis compared with those with PS involvement.

8. Treatment of patients with plasmacytomas should include a bortezomib-based regimen and stem-cell transplantation (SCT) whene-ver possible.

9. Plasma cell Leukemia (PCL) is a very aggressive form of myeloma which definition is currently revisited (5% or more circulating plasma cells).

10. The treatment of PCL should include an intensive regimen such us VTD-PACE immediately followed SCT, including the all-ogeneic procedure, whenever possible.


MARIOBOCCADORO

Mario Boccadoro, MD, is Full Professor and Chief of the Division of Hematology at the Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Italy. He also serves as Coordinator of the Postgraduate degree in Hematology, University of Torino. Prof. Boccadoro is President of the Mul-tiple Myeloma Working Group of the Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA) and member of the European Mye-loma Network (EMN).

Prof. Boccadoro earned his MD from the Uni-versity of Torino, Italy. He completed his Post-graduate degree in Hematology, University of Bologna, and his Postgraduate degree in Internal Medicine, University of Torino. He completed his post-doctoral fellowship at the Free University of Brussels, Molecular Biology Department, Brussels, and was visiting inves-tigator at the Arizona Cancer Center, Section of Hematology, directed by Dr. Brian Durie.

Prof. Boccadoro’s research interests focus on Multiple Myeloma, in particular on therapeu-tic approaches with novel agents, efficacy of high-dose versus conventional chemotherapy, role of prognostic factors, immunosurveillance and immunotherapy, molecular alterations and minimal residual disease, risk assess-ment (through specific scores and markers) and tailored therapy, and he has a track record experience in phase I-II-III clinical trials in Mul-tiple Myeloma. In addition to authoring more than 400 original papers, abstracts, book chapters, and review articles, Prof. Boccadoro is a member of the most important hemato-logical societies, including Società Italiana di Ematologia (SIE), Società Italiana di Ematolo-gia Sperimentale (SIES), American Society of Hematology (ASH), and American Society of Clinical Oncology (ASCO).

University of TurinTurin, Italy

Treatment options for elderly fit patientsFriday, February 1, 16:45 – 17:10

1. Ideally triple combinations are preferred because of their higher efficacy compared to doublets in respect to response rates, depth of response, PFS and OS.

2. In Europe VMP, Rd, MPT, MPR, are appro-ved for frontline therapy in elderly myeloma patients, but the latter two regimens are not used. VRd is submitted for EMA approval and VCd is used in several countries, but is not EMA approved.

3. New data show superior activity of the com-bination of daratumumab with either VMP or Rd for first line therapy in comparison to the chemotherapy backbone alone. Both regi-men are as yet not EMA approved.

4. The optimal duration of therapy has been studied in the FIRST study only. Continuous Rd resulted in significantly longer PFS, but OS was similar in patients scheduled for 18 cycles or for continuous Rd.

5. Patients with excellent tumor response to induction therapy seem to benefit most from continuous treatment.

6. Several investigators deescalate long term treatment with Rd using lower doses of R and discontinuing dexamethasone in order to maintain good/acceptable tolerance.

7. Infectious complications are particularly fre-quent after initiation of therapy, and prophy-lactic antibiotic treatment should be conside-red in those with high risk. (elderly patients, previous episodes of infections)

8. Prophylactic antiviral and anti-thrombotic medication is mandatory in patients on pro-teasome inhibitors and on IMiDs, respecti-vely.

MARIOBOCCADORO


Michele Cavo, MD, is Full Professor of Hae-matology at the University of Bologna, Faculty of Medicine and Surgery, Bologna, Italy, and Head of the “Seràgnoli” Institute of Haema-tology in Bologna. He received his medical degree cum laude from the University of Bolo-gna, where he was also awarded his post-graduate degree in haematology. In 1991 he became Assistant Professor of Haematology, and in 1998 he was appointed Professor of Haematology at Bologna University School of Medicine. From January 2000 to June 2005 and from April 2017 to date Professor Cavo has served as Director of Postgraduate Resi-dency in Haematology at the University School of Medicine in Bologna. He was a member of the board of the Italian Society of Haemato-

logy from 2004 to 2009 and from 2017 to date, and has served as Treasurer of the Society. He is also co-Chair of the Italian Myeloma Network GIMEMA. Main research interests of Professor Cavo focus on multiple myeloma and plasma cell dyscrasias. Professor Cavo has been the Principal Investigator of many academic phase III Italian and European stu-dies for newly diagnosed myeloma patients and has authored many papers published in peer-reviewed journals, including the New England Journal of Medicine, the Lancet, Blood, the Journal of Clinical Oncology, Leuk-emia, British Journal of Haematology, Haema-tologica, and others. He has been a member of the Editorial Board of the Journal of Clinical Oncology and Haematologica.

MICHELE CAVO

Seragnoli Institute of HematologyBologna, Italy

Michele Cavo

University of Bologna, Faculty of Medicine and Surgery, and “Seràgnoli” Institute of Haematology,

Bologna, Italy

Michele Cavo, MD, is Full Professor of Haematology at the University of Bologna, Faculty of Medicine and

Surgery, Bologna, Italy, and Head of the “Seràgnoli” Institute of Haematology in Bologna. He received his

medical degree cum laude from the University of Bologna, where he was also awarded his postgraduate

degree in haematology. In 1991 he became Assistant Professor of Haematology, and in 1998 he was

appointed Professor of Haematology at Bologna University School of Medicine. From January 2000 to June

2005 and from April 2017 to date Professor Cavo has served as Director of Postgraduate Residency in

Haematology at the University School of Medicine in Bologna. He was a member of the board of the Italian

Society of Haematology from 2004 to 2009 and from 2017 to date, and has served as Treasurer of the

Society. He is also co-Chair of the Italian Myeloma Network GIMEMA. Main research interests of Professor

Cavo focus on multiple myeloma and plasma cell dyscrasias. Professor Cavo has been the Principal

Investigator of many academic phase III Italian and European studies for newly diagnosed myeloma

patients and has authored many papers published in peer-reviewed journals, including the New England

Journal of Medicine, the Lancet, Blood, the Journal of Clinical Oncology, Leukemia, British Journal of

Haematology, Haematologica, and others. He has been a member of the Editorial Board of the Journal of

Clinical Oncology and Haematologica.

Strategies for optimizing maintenance treatmentFriday, February 1, 14:30 – 14:55

1. Achieving undetectable minimal residual disease (MRD) and sustaining a negative MRD status as much long as possible have been shown to be the most relevant pre-dictors for long-term favorable outcomes of multiple myeloma (MM) patients.

2. Maintenance therapy or continuous expo-sure to a single agent or multi-drug combi-nations aimed at keeping under control resi-dual tumor cells after therapy are a widely used strategy to prevent or delay disease progression (PD).

3. Due to their immunomodulatory properties and ease of oral administration, thalidomide and lenalidomide were the first novel agents explored as maintenance therapy after auto-logous stem cell transplantation (ASCT).

4. Lenalidomide is by now the only novel agent approved by EMA for maintenance therapy after ASCT, based on the extended pro-gression-free survival (PFS) reported in two phase III studies comparing lenalidomide vs placebo or observation, and the longer over-all survival (OS) reported in one of them.

5. A recent meta-analysis including a third study confirmed that the PFS and OS bene-fit from lenalidomide maintenance therapy were retained across many prespecified subgroups of patients and outweighted the risk of developing a second primary malig-nancy.

6. Although phase III studies comparing bor-tezomib maintenance versus placebo or observation are lacking, in one trial borte-zomib was associated with extended post-ASCT PFS and OS in comparison with thali-domide, particularly in patients with del(17p) who are likely to not benefit the most from lenalidomide therapy.

7. The second generation oral proteasome inhibitor ixazomib given for up to 2 years sig-nificantly prolonged PFS in comparison with placebo after ASCT, thus providing a valua-ble treatment alternative to patients who are not able to tolerate lenalidomide.

8. Analyses aimed at quantifying the added value of continuous exposure to the monoc-lonal antibodies daratumumab, elotuzumab and isatuximab, either single or combined with other agents, in both newly diagnosed and relapsed/refractory MM patients are cur-rently ongoing.

9. The optimal duration of maintenance/conti-nuous therapy (fixed vs undefinite until PD or toxicity) and the best choice of agents (single vs combined) to be used in the overall patient population and in selected subgroups at dif-ferent risk still remain unanswered questions which need to be addressed in future pro-spective clinical trials incorporating genomics and assessment of minimal residual disease as possible drivers of treatment strategies.

MICHELE CAVO


Professor Cook, MBChB, PhD, is a Consul-tant Haematologist at University Hospitals Bir-mingham, specialising in plasma cell disorders and stem cell transplant in one of the busiest plasma cell practices in the UK. He received his medical degree from the University of Bris-tol and was awarded his PhD in the Immuno-genetics of Bone Marrow Transplantation in 2009 by the University of Birmingham. He is Trust Lead Cancer Clinician and Associate Di-rector of Research at UHB. He has recently been made an Honorary Professor in the Ins-titute of Cancer and Genomic Sciences at the University of Birmingham.

His research interests include areas related to multiple myeloma, particularly renal impair-ment secondary to gammopathy. He is also in-terested in ensuring genomics is a routine part of Cancer practice, having developed regional genomic tumour boards for all Cancer sites in the West Midlands.

He is part of the Birmingham group that have published pre-clinical and clinical work on the nature of renal impairment in patients with my-eloma and other gammopathies including the EuLITE study evaluating the role of high cut-off dialysis in newly diagnosed myeloma pa-tients requiring dialysis. Data from this study will be presented at the meeting.

He is vice-chair of the UK Myeloma Re-search Alliance and has been CI and local PI on multiple national clinical trials and is Co-Chief Investigator with Professor Kwee Yong for the forthcoming UK national study Myeloma XV. He is author/co-author on 60 peer- reviewed publications, an article reviewer for several journals, has been an abstract re-viewer for ASH and BSH and also a grant re-viewer.

MARKCOOK

University Hospitals BirminghamBirmingham, United Kingdom

Renal disease in multiple myeloma: Pathophysiology and treatmentWorkshop: Friday, February 1, 11:25 – 12:15 and 15:55 – 16:45

1. Renal impairment in is common in myeloma- recent population studies have clarified the incidence of severe renal impairment requi-ring dialysis. (Evison et al. Br J Haematol 2018;180:588-9)

2. The mechanism of renal impairment in mye-loma is better understood than in previous years, with circulating free light chain levels in excess of 500mg/mL being significantly associated with cast nephropathy. (Sanders et al. J Am Soc Nephrol 2009;4:745-754)

3. Mechanical removal of serum free light chains has limited use in cast nephropathy. Trials of plasma exchange in myeloma have failed to show any benefit. (Clark et al. Ann Intern Med 2005;143:777-84)

4. Trials of advanced dialysis techniques have not shown a clear benefit for mechanical removal of serum free light chains. (Bridoux et al. JAMA2017;318:2099-2110 and EuLITE data to be presented)

5. Early, sustained reduction in serum free light chains is key to renal recovery. (Hutchison et al. J Am Soc Nephrol 2001;22:1129-36)

6. Treatment of myeloma at diagnosis in pati-ents with severe renal impairment is currently based on the proteasome inhibitor bortezo-mib, inducing rapid reduction in serum free light chain levels. (IMWG 2016 J Clin Oncol)

7. Stem cell transplantation in the renally impai-red patient can be delivered safely.

8. Outcomes for patients presenting with severe renal impairment have improved dra-matically in the last decade. (Dimopoulos et al. Ann Oncol 2014;25:195-200)

9. Unanswered questions include the role of renal transplantation in those patients who have an excellent myeloma response but remain on dialysis.

MARKCOOK


Hermann Einsele, MD, FRCP, is Full Profes-sor of Internal Medicine and has been Director of the Medizinische Klinik und Poliklinik II of the Julius Maximilian University, Würzburg, Germany since 2004.

Following his medical training at the Univer-sities of Tübingen, Manchester, and London, Professor Einsele became a research fellow in the Department of Haematology, Oncolo-gy, Rheumatology, and Immunology at the University of Tübingen, Germany. He was board certified in Internal Medicine in 1991 and in Haematology/Oncology in 1996. In 1999 was promoted as an Associate Profes-sor. He is a visiting professor at the Fred Hut-chinson Cancer Research Center in Seattle, WA, USA, and at the City of Hope Hospital, Duarte, CA, USA.

2011-2015 Hermann Einsele was Vice Dean of the Faculty of Medicine of the University of Würzburg, since 2015 he is Vice President of the University of Würzburg. In 1999, he be-came Chairman of the German Study Group Multiple Myeloma. In 2003, he received the van Bekkum Award, the highest Annual Euro-pean award for research in the field of stem cell transplantation. In 2011 he was elected as an Honorary Fellow of the Royal College of Patho-logists (London), in 2012 Nobel Lecturer Stem Cell Biology/ Transplantation, Nobel Forum Ka-rolinska Institute, and 2014 Member of the Aca-demy of Sciences and Literature, Mainz.

Prof. Einsele is expert in the field of multiple myeloma, stem cell transplantation and ad-optive immunotherapy in haematological and oncological patients.

HERMANNEINSELE

University Hospital WürzburgWürzburg, Germany

Strategies for optimizing CAR-T cell and other cellular therapiesSaturday, February 2, 11:35 – 12:00

1. BCMA CAR T-cells have been administe-red in clinical trials with surprising efficacy. Data on the most recent BCMA CAR T-cell trials will be presented.

2. BCMA-directed bispecific antibodies have shown promising activity.

3. New strategies to improve the safety and efficacy of T-cell redirection strategies will be discussed.

4. T-cell persistence and target antigen loss are major determinants of the success of T-cell redirection strategies.

5. New targets will be important to improve efficacy of CAR T cells in MM.

6. Dual targeting might improve safety and efficacy of T cell redirection strategies.

HERMANNEINSELE


Dr. Francesca Gay is an hematologist at the Myeloma Unit, Division of Hematology, Azienda Ospedaliero Università Città della Salute e della Scienza, in Torino, Italy.

She completed her medical degree in 2004 and her fellowship in hematology in 2008 at the University of Torino, Italy. She obtained her PhD in Medicine and Experimental The-rapy in 2014.

Dr Gay’s special interest is the treatment of patients with multiple myeloma and associa-ted disorders, and she is coordinating and working on the design and development of clinical trials from multiple myeloma, in the GIMEMA and EMN group.

She is a member of EMN, EHA and ASH. She is author and co-author of several papers pu-blished in peer reviewed journals, as well as reviewer for several journals including Leuk-emia and Hematologica.

FRANCESCAGAY


Diagnostic workup in patients with paraproteinemiaFriday, February 1, 11:00 – 11:25

1. Diagnostic work up in patients with para-proteinemia aims to discriminate between monoclonal gammopathy of undetermined significance (MGUS), smouldering multiple myeloma (SMM), multiple myeloma (MM) and solitary plasmocytoma.

2. Standard diagnostic work-up include: blood test (complete blood cell count, renal function, serum calcium levels, total serum protein, serum protein electrophoresis, serum immu-nofixation, nephelometry of serum immuno-globulin, serum free light chain measurement) and urine test (24h total protein evaluation, urine immunofixation, urine electrophoresis).

3. Bone marrow (BM) evaluation with BM aspi-rate and/or biopsy is needed. Clonality should be assessed by showing light chain restriction on flow cytometry, immunochemistry or immu-nofluorescence. A significant conversion rate of bone marrow plasma cell from <10% with BM aspirate to >10% with biopsy has been reported. IMWG recommends the higher value being used in case of discrepancy.

4. Peripheral blood smear and immunopheno-type should be performed in case of suspec-ted plasma cell leukemia.

5. Imaging evaluation with whole body low dose CT, PET-CT, or skeletal survey if the other techniques are not available is needed to exclude the presence of lytic lesions.

6. To confirm the absence of bone disease in the absence of lytic lesions detected by whole body low dose CT, PET-CT, or skeletal sur-vey, whole body MRI should be performed. If whole body MRI is not available, MRI of

the spine and pelvis is recommended. MRI of the spine is also recommended in case of suspected spinal cord compression.

7. In patients with symptomatic MM, prognostic baseline evaluation should include FISH ana-lysis on BM. Minimal panel evaluation should include del17p and t(4;14). Other chromoso-mal abnormalities with prognostic impact are t(14;16), t(14;20) and gain1q.

8. Prognostic baseline evaluation in symptoma-tic MM comprises also serum albumin and ß2microglobulin to define International Sta-ging System (ISS) Stage, and LDH level to define Revised-ISS Stage.

9. Modification of Diet in Renal Disease (MDRD) equation is recommended for evaluation of renal failure (RF) in MM patients with stabi-lized serum creatinine. RF can be classified in 5 stages according to the Kidney Disease Improving Global Outcomes classification. In acute RF, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment.

10. Many mechanisms can contribute to RF in MM. The most frequent are cast nephropathy, light chain deposition disease and amyloido-sis. Evaluation of urinalysis to discriminate between selective and non-selective proteinu-ria as well as presence of nephrotic syndrome is helpful to discriminate between these pos-sible causes. Renal biopsy should be consi-dered to confirm the diagnosis in case of any doubt.

FRANCESCAGAY


Priv.-Doz. Dr. med. Dr. biol. hom. Dirk Hose is physician in the Department of Hematology, Oncology, and Rheumatology at the Universi-ty Hospital Heidelberg and head of the Multip-le Myeloma Research Laboratory (LfM) which he founded. He has graduated in physics and medicine and holds a degree in human biology (PhD equivalent) and medicine (Dr. med., PhD equivalent). The Priv.-Doz. title comprises the rights of a professorship in the US. The LfM, currently with a team of 14 coworkers, focuses on the molecular characterization and pathoge-nesis of plasma cell dyscrasias and develop-ment of novel therapeutic compounds and stra-tegies (e.g. EM801, a novel first-in-class BCMA T-cell bispecific antibody; Seckinger et al., Can-cer Cell 2017). Aim is an effective, risk-adap-ted, and personalized myeloma treatment with subsequent cure of the disease. The laborato-ry has generated one of the largest datasets worldwide regarding gene expression (in part together with Prof. Bernard Klein, Montpellier, France) and interphase fluorescence in situ hy-bridization (with Prof. Anna Jauch, Heidelberg) of patients with plasma cell dyscrasias. Results are reported in clinical routine to patients and clinicians. The work resulted in more than 120 peer-reviewed publications and longstanding national and international collaborations, e.g. 6th (MSCNET) and 7th (OVER-MyR) EU-fra-mework program.

Dirk Hose has been vice speaker for Heidelberg within the three university grant initiative SFB/TRR79 since 2010 and speaker since 2017. He was awarded e.g. the IMW Young Investigator Award, the Ludwig Strauss Habilitation award for excellence in research of SFB/TRR79, and a honorary professorship of the University Hos-pital for TCM in Nanjing, China.

Dirk Hose is member of the German (DGHO) and American (ASH) societies of hematology, the international myeloma society (IMS), and invited member of the International Myeloma Working Group (IMWG), as well as of peer-re-view panels for leading journals including Lan-cet Oncology and Blood, and international grant review bodies for plasma cell diseases. He has been invited to participate as member of scien-tific program committees/session chairs/invited speakers at the International Myeloma Work-shop, annual meetings of the ASH, European Hematology Association (EHA), and DGHO. He is participating in and conduction trials wit-hin the German-Speaking Myeloma Multicen-ter Group (GMMG) whose board-member he is. He performs myeloma clinics and research since 2002.

DIRKHOSE

University Hospital Heidelberg Heidelberg, Germany

From MGUS to multiple myeloma: Insights into the pathophysiologyFriday, February 1, 08:20 – 08:45

1. Definitions. Malignant plasma cell diseases are delineated in monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM) and multiple mye-loma. MM-patients per definition either show signs or symptoms of the disease termed as CRAB-criteria (hypercalcemia, renal insuffi-ciency, anemia, or osteolytic bone disease; i.e. end-organ damage), or biomarkers of frequent progression to these, i.e. a free light chain ratio (regarding the involved chain) above 100:1, more than one focal lesion in MRI, and/or more than 60% (sixty) clonal plasma cells on bone marrow examination, the so-called SLiM-criteria (Rajkumar et al., Lancet Oncol 2014).

2. MGUS and SMM are delineated by tumor mass only. This delineation is somehow necessarily artificial. Biologically, there is no difference in a patient with 11% plasma cell infiltration in bone marrow aspiration (defined as SMM) or 9% (defined as MGUS).

3. The term asymptomatic myeloma (AMM) can be used for patients with SMM and those MM-pa-tients with absence of CRAB-criteria. Both do not show signs or symptoms of the disease.

4. Within 5 years, MGUS progresses with 5% probability, AMM with 50% probability to sym-ptomatic myeloma (Kyle et al. NEJM 2007, 2018).

5. Molecularly, there is no aberration exclusive to MM not already present in MGUS or AMM. This includes chromosomal aberrations detected by iFISH (e.g. del17p1 and 1q21-

gain) or by next generation sequencing (e.g. Ras-, FAM46C-mutations): all can already be found at MGUS and AMM stage.

6. The frequency of these alterations however is different between the entities: progres-sion-associated alterations (e.g. del17p13, 1q21-gain, Neben et al. JCO 2013, Seckin-ger et al. Blood 2016 128:235) increase in prevalence significantly from MGUS to AMM to MM. However: in longitudinal samples, progression-associated alterations are very rarely gained, and can even be lost. The de novo acquisition of these alterations is thus not necessary for progression.

7. In turn, molecular alterations at diagnosis of AMM, tumor mass, and plasma cell accumu-lation rate determine progression (Seckinger et al. Blood 2016 128:235)). These are in other words “up-front” alterations.

8. How can it then be that some patients do not progress from MGUS / AMM for many years? The most likely answer is because in most case exactly those patients progress whose myeloma cells already at the stage of diagno-sis (i.e. MGUS / AMM) stage carry those alte-rations, whereas the others do not.

9. The lack of proven increase in genetic hete-rogeneity from AMM to MM implies that this cannot be taken as indication for early treat-ment.

10. For patients fulfilling the SLiM-criteria only (i.e. without end-organ damage), this can be seen as indication to reflect on treatment, but not necessarily immediately start it.

DIRKHOSE


Alessandra Larocca, MD,PhD is a Consul-tant physician of the Division of Hematology at the Department of Hematology-Oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She studied Medicine at the University of Milano (1996-2001), and completed her resi-dency in Hematology at the same Institution (2001-2005).

In 2014 she obtained her PhD in Pathology and Experimental Oncology at the University of Torino. She is coordinating and working on the design and development of clinical trials for multiple myeloma developed in the De-partment of Hematology. She is author and co-author of papers and books published in peer-reviewed journals. Her interest is in multiple myeloma and its treatment including new drugs, with special focus on clinical trials and treatment of elderly patients.

ALESSANDRALAROCCA


Management of elderly, unfit and frail patientsFriday, February 1, 17:10 – 17:35

1. Multiple myeloma (MM) is a neoplastic disease of older adults, with a higher incidence in elderly patients. The prevalence of myeloma is likely to increase due to the extended survival and the growing life expectancy of the general population.

2. Much progress has been made in the past few years thanks to the introduction of new drugs, with an improvement in the prognosis of elderly patients. Nevertheless, such improvement is less marked compared to younger patients, pro-bably due to biological aging. Furthermore, the currently approved treatment regimens for pati-ents with multiple myeloma who are not eligible for an autologous stem stem-cell transplantation were tested in clinical trials with stringent inclu-sion criteria.

3. Aging is associated with a high prevalence of frailty, that is, a state of increased vulnerability to stressors due to a critical decline in physiologic reserves. Elderly people may be categorized as fit or frail according to clinical, functional and cog-nitive criteria. The presence of frailty may compli-cate the management and outcome of myeloma patients.

4. To date, the choice of treatment of myeloma patients has focused primarily on chronological age and performance status as markers of frailty. However, the elderly population is highly hetero-geneous, and improved assessment strategies are needed to define the frailty profile of patients and provide them with the most adequate treat-ment, thus avoiding the over-treatment of frail patients and the under-treatment of fit patients.

5. The International Myeloma Working Group (IMWG) developed a score to identify frail pati-ents with inferior overall survival (OS) and pro-gression-free survival (PFS), higher incidence of grade 3/4 non-hematologic toxicity and discon-

tinuation rate. The score is based on age (≤75, 76-80 or >80 years), the Charlson Comorbidity Index (≤1 or >1), the Activities of Daily Living (ADL, >4 or ≤4) and instrumental ADL (IADL, >5 or ≤5) have been validated in a separate cohort of patients. The IMWG frailty score is the current gold standard score to evaluate patient status.

6. On the basis of the IMWG frailty score, patients can be stratified into a fit, intermediate or frail group. In frail MM patients, anti-MM drugs may cause more side effects and subsequent discon-tinuation of therapy, with a negative impact on outcome.

7. Rd and VMP are the current standards of care for older patients with newly diagnosed myeloma. To date, there have been no prospective trials eva-luating geriatric assessment–driven treatments in elderly patients with newly diagnosed MM.

8. Frail patients need effective tailored treatments to better control the disease while minimizing the risk of toxicity and treatment discontinuation. The selection of therapy should be based on the risk of toxicity and the capacity of patients to tolerate treatment.

9. The choice of treatment – transplantation, tri-plets, doublets, or reduced-dose therapies including novel agents – should depend on the patient’s fitness status (fit, intermediate-fit, or frail). Second-generation novel agents have also been evaluated both at diagnosis and as salvage therapy in the elderly, and these new agents cer-tainly represent a further step forward in the treat-ment armamentarium for elderly patients with multiple myeloma.

10. Additional studies are needed to define more precise geriatric assessment–directed treatment selection.

ALESSANDRALAROCCA


Dr. Heinz Ludwig is Professor of internal medicine and haemato-oncology and chair of the Wilhelminen Cancer Research Institute at the Department of Medicine I, Centre for Oncology and Haematology, Wilhelminenspi-tal, Vienna, Austria.

Professor Ludwig’s research interests focus on haematology and medical oncology and in particular on multiple myeloma and related disorders. He has contributed to the unders-tanding of mechanisms of drug response and myeloma stroma interaction, has designed and conducted investigator initiated trials and actively contributed to cooperate group and industry-sponsored trials. Another major research area relates to the pathophysiology and treatment of cancer-associated anaemia. Professor Ludwig’s has a strong interest

in improving the quality of cancer care by promoting medical training and research, empowering patients, improving patient infor-mation and alerting society to patients’ needs.

Professor Ludwig has published a large number of scientific manuscripts in presti-gious medical journals and serves as peer reviewer of several international journals. Professor Ludwig has served as president of the European Society for Medical Oncology (ESMO) and has been member of the Inter-national board of ASCO and is the founder of the ESMO Foundation. Professor Ludwig is board member of the International Myeloma Foundation and a member of the IMWG. In recognition of his influential work, he was the recipient of the Fifth Annual Robert A. Kyle Lifetime Achievement Award.

HEINZLUDWIG

Wilhelminen Cancer Research InstituteVienna, Austria

Sequencing in relapsed / refractory diseaseSaturday, February 2, 10:50 – 11:15

1. The clinical pattern at relapse resembles the situation at diagnosis. Patients with sympto-matic disease at first presentation usually are symptomatic at relapse, while biochemical relapse usually is encountered in good risk patients who were asymptomatic at diagno-sis.

2. Relapse treatment should be initiated without delay in patients with high risk disease and/or symptoms, while in those with biochemi-cal relapse and without symptoms, treatment can be delayed for some time, provided those patients can closely been monitored.

3. Selection of treatment for an individual patient depends on patient’s age, fitness and comorbidity, biology of the disease (aggressive, cytogenetic-high risk, or non-aggressive), quality of response, duration of response and tolerance to previous therapy, and on the availability of drugs/treatment options.

4. At first relapse, ASCT is a reasonable option in transplant-eligible patients with long PFS after the initial ASCT, or as second line the-rapy after induction with conventional treat-ment. In all others, change of drug class is recommended, but re-treatment is a feasible option in patients with good response and tolerance of previous treatment.

5. Several recent randomized trials revealed significant superiority of three-drug regimens including a novel drug (carfilzomib, ixazomib, elotuzumab, daratumumab) compared to an established two drug (Rd or Vd) backbone in patients with 1-3 prior treatment lines.

6. Pomalidomide with dexamethasone and panobinostat with Vd have been approved for patients with ≥ 2 prior lines of therapy inclu-ding lenalidomide and bortezomib. Adding elotuzumab, bortezomib, or cyclophospha-mide to pomalidomide dexamethasone has been shown to be superior to the original doublet regimen.

7. Patients with high-risk cytogenetics, as defi-ned by FISH or gene arrays should receive regimens incorporating a proteasome inhibi-tor and possibly a monoclonal antibody, alt-hough in this setting, the impact of the mAbs is less evident.

8. Selinexor, an XP01 inhibitor, and venetoclax, have shown remarkable activity in RRMM and likely will be approved in due time. Bites (bi-specific antibodies), antibody-drug conju-gates, CAR-T cells and other therapies will be covered in other sessions.

9. There are few data on the optimal length of treatment duration and on maintenance therapy. Experts recommend continued treatment until progression or intolerance in patients with poor risk features, while in those with good prognosis, treatment may be discontinued after achievement of a durable remission.

10. In patients failing to several lines of therapy, alkylator-based therapy such as cyclophos-phamide-prednisolone or continuous infusion treatment with DCEP, DT-PACE, or inclusion in a clinical trial may be valuable options.

HEINZLUDWIG


Dr. María-Victoria Mateos, MD, PhD, is Con-sultant Physician in the Haematology Depart-ment and Associate Professor of Medicine at the University of Salamanca, Spain. She is the director of the Myeloma Program and coordi-nates the Clinical Trials Unit in Salamanca’s University Hospital Haematology Department. She serves as coordinator of GEM (Spanish Myeloma Group), with direct involvement in the design and development of clinical trials. She has coordinated many clinical trials in el-derly and smouldering MM patients that have profoundly influenced current options for trea-ting these patient populations.

She is also a member of the IMWG (Interna-tional MM Working Group), IMS (International MM Society), EHA and ASH. She has publis-hed over 200 papers in peer-reviewed inter-national journals, some of which have become key references in the Multiple Myeloma field. She is Associate Editor of myeloma in Annals of Haematology since 2011 and has acted

as a reviewer for top journals such as NEJM, Lancet and Lancet Oncology. Among her invi-ted presentations, she has recently contribu-ted to the educational sessions of EHA 2012, ASH 2013, ASCO 2015, EHA 2016, ASCO and ASH 2017.

She has served on the EHA’s Scientific Pro-gram Committee and Advisory Board since 2013 until 2017, and on the ASH Scientific Committee on plasma cell diseases in 2015-2017.

She is a Councillor on the EHA Board since 2015 for a four-year mandate, member of the Steering Committee for the Society of Hema-tologic Oncology (SOHO), member of the IMS board and member of the European School of Haematology (ESH) Scientific committee. She has published over 200 original papers in international journals. Her areas of interest in-clude multiple myeloma, the biology of plasma cells and the news drugs development.

MARIA-VICTORIAMATEOS

Hospital Universitario de SalamancaSalamanca, Spain

Risk stratification of smoldering myeloma and recommendations for managementFriday, February 1, 13:40 – 14:05

1. Smoldering Myeloma is defined by the pre-sence of a M-component of at least 3 g/dL and/or plasma cell bone marrow infiltration between 10 and 60% without any myelo-ma-defining event.

2. Overall, the risk of progression to Myeloma is 10%.

3. However, there are different subgroups of patients with different risk of progression to myeloma.

4. The International Myeloma Working Group (IMWG) updated the definition of Myeloma in 2014 including asymptomatic patients with an imminent risk of progression to myeloma, 80% within the first year from dia-gnosis (plasma cell bone marrow infiltration ≥60%, serum free-light chain ratio ≥100 and/or more than 1 focal lesion in whole body magnetic resonance imaging).

5. According to the Mayo Clinic model, the pre-sence of a M-component of at least 3 g/dL and at least 10% of plasma cell bone mar-row infiltration identifies a subgroup in which the risk of progression to Myeloma is 50% at 2 years.

6. The Spanish model is able to identify another high risk subgroup of smoldering myeloma

when the percentage of aberrant plasma cells in the bone marrow by flow cytometry is of at least 95% plus immunoparesis.

7. Both models have been so far validated in a clinical trial but, at the same time, many different models to evaluate the risk of pro-gression to myeloma have been developed over the last few years.

8. This new models include positive uptake in PET-CT, cytogenetic or molecular abnor-malities, evolving pattern of the M-compo-nent and decrease in Hb.

9. This heterogeneity, therefore, represents a challenge and a universal model should be defined.

10. Although the standard of care continues being observation, the Spanish group demonstrated that early treatment with lenalidomide plus dexamethasone in high risk smoldering myeloma patients is able to delay the progression to myeloma with a significant benefit in overall survival and this has been the starting point to conduct more than 50 clinical trials and some of them, with curative intention.

MARIA-VICTORIAMATEOS


Giampaolo Merlini received his medical de-gree and specialized in Hematology and in Laboratory Medicine at the University of Pavia. He was trained by Prof. Jan Walden-ström and Prof. Elliott Osserman in the study of monoclonal gammopathies and systemic amyloidosis. He is the Director of the Cen-ter for Research and Treatment of Systemic Amyloidosis, University Hospital Policlinico San Matteo, and the Director of Research of the University Hospital. He is full Professor of Clinical Biochemistry, Department of Mole-cular Medicine, University of Pavia, Italy. He was President of the International Society of Amyloidosis from 2005 to 2010. He received several awards, including the Jan G. Wal-denström Award, the 2017 Ham-Wasserman Lecture of the American Society of Hematolo-gy and the Robert Kyle Award in 2018.

Dr. Merlini’s research interests include the pathogenesis, natural history, diagnosis and treatment of monoclonal gammopathies, in particular immunoglobulin light chain amyloi-dosis. His recent research focuses on the in-vestigation of molecular mechanisms of car-diac damage, on biomarkers for assessing prognosis and response to therapy and on the development of novel therapeutic agents and treatment designed in the light of advan-ces in the understanding of the molecular mechanisms of these diseases. He is princi-pal investigator for several research projects in this field.

GIAMPAOLOMERLINI

Fondazione IRCCS Policlinico San MatteoPavia, Italy

New developments in amyloidosisSaturday, February 2, 12:30 – 12:55

1. The molecular mechanisms underlying amyloid formation indicate that early dia-gnosis and prompt and profound reduction of the amyloid precursor are vital.

2. Early diagnosis, risk assessment and treat-ment monitoring are based on biomarkers and imaging.

3. Cardiac amyloidosis caused by wild-type transthyretin is more common than previ-ously thought in elderly man: scintigraphy and amyloid typing help in assessing the diagnosis.

4. The biology of the amyloidogenic clone suggests the appropriate therapy.

5. The mainstay of therapy is the rapid and profound suppression of the production of the amyloidogenic light chain.

6. Minimal residual disease may play a role in impeding the recovery of organ damage.

7. Immunotherapy targeting the clone provi-des unprecedented hematology response rate and is a game changer. Target thera-pies are also emerging.

GIAMPAOLOMERLINI


Philippe Moreau, MD, is Head of the Hema-tology Department at the University Hospital of Nantes, France. He specializes in clinical hematology, with a particular focus on multip-le myeloma and its treatment with high-dose therapy and novel agents. Dr Moreau was appointed University Professor of Clinical Hematology at Nantes Faculty of Medicine in 2003.

Prof. Moreau was a member of the organi-zing committee for the 2011 International Myeloma Workshop, in Paris. Prof. Moreau is currently a member of the administration council of the Intergroupe Francophone du Myélome (IFM), and he was chairman of the IFM from 2006 through 2009. He is a member

of the steering committee of the International Myeloma Working Group.

Prof. Moreau is widely published, with more than 300 per-reviewed articles and reviews that have appeared in high impact factor jour-nals including New England Journal of Me-dicine, Journal of Clinical Oncology, Lancet, Lancet Oncology, Blood or Leukemia. He is frequently invited speaker at international he-matologic oncology meetings. He is member of the Editorial Board of the Journal of Clinical Oncology, Blood, and Blood Cancer Journal.

Prof. Moreau received in 2018 the Robert A. Kyle lifetime achievement award.

PHILIPPEMOREAU

University Hospital Hôtel-DieuNantes, France

Optimizing induction and consolidation therapyin TE patientsFriday, February 1, 14:05 – 14:30

PHILIPPEMOREAU

1. Three-drug combinations including at least bortezomib and dexamethasone are cur-rently the standard of care prior to ASCT.

2. In Europe, VTD and VCD are the most preferred regimens. VRD, when approved, will be probably widely used.

3. KRD, currently being evaluated in ongoing phase III trials, is associated with high res-ponse rates, but is not approved in the EU.

4. MRD negativity after induction will become an important end-point.

5. The combination of monoclonal antibo-dies, either elotuzumab or daratumumab, to standard induction regimens, is currently being evaluated in ongoing phase III trials.

6. Consolidation following ASCT is improving the depth of response.

7. Ongoing trials (EMN02/H095 evaluating the role of 2 VRD cycles; and BMT CTN 0702 evaluating the role of 4 VRD cycles, or tandem ASCT) will clarify the impact of consolidation.

8. Tandem ASCT may be proposed outside clinical trials in patients with high-risk cyto-genetics.


Mohamad Mohty is full Professor of Hemato-logy and head of the Hematology and cellulartherapy Department at the Saint-Antoine Hos-pital and Sorbonne University (Paris, France). Professor Mohty obtained his medical degree from the University of Montpellier, France, and his PhD from the University of Marseille, France. He also undertook post-doctoral work at the Hematology Department, Impe-rial College, Hammersmith Hospital, London, UK.

Professor Mohty’s is also head of a transla-tional research team (INSERM team N°7) at the Saint-Antoine Research centre in Paris and his research is focused on the pathophy-siology and immunobiology of normal and pathological antigen-presenting cells, espe-cially the impact of novel immunomodulatory agents such as proteasome inhibitors, IMiDs and hypomethylating agents.

He has a special clinical focus on the develop-ment of reduced-toxicity conditioning regi-mens, immunotherapy and different aspects of therapy of acute leukemia and multiple myeloma.

Professor Mohty is past-president of the Euro-pean Society for Blood and Marrow Transplan-tation (EBMT), and the current chairman of the Acute Leukemia Working Party of EBMT. He is also the founder and chairman of the “Internatio-nal Academy for Clinical Hematology. He serves on the board of the EBMT, and the “Intergroupe Francophone du Myelome” (IFM). He is a mem-ber of the American Society of Hematology, Ame-rican Society for Clinical Oncology, American Society for Blood and Marrow Transplantation, European Hematology Association, and EBMT.

Professor Mohty has published more than 550 peer-reviewed articles in the field of stem cell transplantation, leukemia and myeloma, in dif-ferent hematology and immunology journals. He also serves as Editor-in-Chief of the jour-nal Bone Marrow Transplantation, as Associate Editor for Leukemia, European Journal of Hae-matology and Blood Cancer Journal, as mem-ber of the editorial board of Haematologica, and as a regular reviewer in different immuno-logy, hematology, and cancer journals such as the New Engl. J Med, Blood, J Clin Oncol, The Lancet, Lancet Oncology, Lancet Haematolo-gy, Nature Reviews, etc.

MOHAMADMOHTY

Saint-Antoine HospitalParis, France

Transplantation and cellular therapies in MMBreakfast Meeting, Saturday, February 2, 07:45 – 08:15

1. Autologous stem cell transplantation (auto-SCT) remains the standard of care in young and fit myeloma patients.

2. Double auto-SCT can likely improve the outcome of high risk patients.

3. The optimal high-dose chemotherapy prior to auto-SCT is melphalan 200mg/m²; howe-ver, some trials suggested a potential role for the busulfan-melphalan combination.

4. The use of consolidation after auto-SCT is a matter of debate.

5. Maintenance therapy with lenalidomide is the standard of care after auto-SCT, but proteasome inhibitors can be indicated in high risk patients.

6. The role of auto-SCT is likely to be challen-ged in the future, with the advent of modern regimens allowing to achieve deep MRD negativity without the need for high-dose chemotherapy.

7. CAR-T cells are being investigated with promising results in highly advanced and refractory patients, but long term follow-up is still needed.

8. BCMA is the most widely studied target for the use of CAR-T cells in myeloma

9. The optimal CAR-T cell construct is yet to be defined in terms of efficacy and safety.

10. CAR-T cells are being tested in the frontline setting with or without auto-SCT.

MOHAMADMOHTY


Dr. Enrique M. Ocio, MD, PhD, currently is the Head of the Hematology Department of the University Hospital “Marqués de Valdecilla” in Santander (Cantabria-Spain). He graduated in Medicine in the University of Salamanca and completed his residency in Haematology and obtained the PhD in the University Hos-pital of Salamanca. Later on, he enjoyed a one-year post-doctoral stay in Dana Farber Cancer Institute (Harvard University, Boston, MA. USA), working in the development of no-vel drugs for multiple myeloma.

In the last years he has combined his tasks as a physician in Salamanca, coordinating the Clinical Trials Unit of the department and the Phase I Trials Unit of the hospital, with his research work in the Cancer Research Center of the University of Salamanca as the

responsible of the New Drugs Development Unit in Hematologic Malignancies. He has published over 100 original papers in inter-national journals. His main areas of interest are the study of the biology of multiple myeloma and other haematological malignancies such as acu-te myeloid leukemia or B lymphoproliferati-ve disorders; and the development of novel antitumoral drugs from the preclinical setting to early phases clinical trials. Among these he has focused on the study of the activity and mechanism of action and resistance of several drugs such as proteasome inhibitors, IMIDs or deacetylase inhibitors, and the study of the immune system and the evaluation of novel immunotherapeutic strategies.

ENRIQUEOCIO

Hospital Universitario Marqués de ValdecillaSantander, Spain

Innovative drugs for myeloma therapySaturday, February 2, 11:15 – 11:35

1. Treatment of MM has substantially changed in the last years with the recent approval of drugs with novel mechanisms of action such as monoclonal antibodies. However, novel drugs with novel mechanisms are still needed for refractory patients.

2. The improvement in the understanding of MM pathogenesis leads to the discovery of novel targets that could be active against MM plasma cells.

3. The microenvironment has a key influence in the development and progression of MM and it should be considered as a key target for novel agents.

4. Novel generation of the already approved drugs are being explored both preclinically and clinically. Some examples are novel alkylators such as melflufen, novel IMiDs derivatives such as the so called “CelMods” or novel proteasome inhibitors such as oprozomib or marizomib.

5. RAS pathway is mutated in around 50% of patients and it might be a promising thera-peutic target. Therefore, some downstream effects are targets for therapeutic interven-tion with ERK inhibitors, AKT inhibitors or PIM kinase inhibitors.

6. One of the strategies with more promise is the targeting of Bcl-2 family members.

In this regard, the Bcl2 inhibitor venetoclax has demonstrated activity in heavily pre-treated patients, both alone and in com-bination with bortezomib. More recently, several Mcl-1 inhibitors are also being eva-luated both preclinically and clinically.

7. Selinexor in combination with dexamet-hasone, has demonstrated activity in pen-ta-refractory patients, through the inhibition of XPO1, a protein that exports different proteins from the nucleus of the tumor cell.

8. Another field of development with good preliminary results, consist on the novel immunotherapeutic approaches such as MM targeted ADC, CAR-T cells or agents designed to activate the immune system or block immune checkpoints.

9. The search for biomarkers predicting sen-sitivity or resistance to a given agent is of upmost importance, in the current scenario. In line with this, venetoclax has demonstra-ted to be particularly effective in patients carrying the t(11;14).

10. The future is optimistic in MM treatment, and it will probably rely in the use of the optimization of the currently available back-bones, in combination with novel targeted agents, probably in selected population based on the use of biomarkers.

ENRIQUEOCIO


Doctor Bruno Paiva is a research fellow of the departments of Haematology and Immu-nology at the Clinica Universidad de Navarra (CUN) and Centro de Investigaciones Medi-cas Aplicadas (CIMA), Pamplona, Spain.

Dr Paiva is also the director of the Flow Cy-tometry Core and scientific coordinator of CIMA LAB Diagnostics, the laboratory dia-gnostic core of the University of Navarra. He graduated in pharmaceutical sciences at the University of Coimbra, Portugal, in 2007. He then spent a training period with Professor Alberto Orfao focusing on immunophenoty-pic in acute myeloid leukaemia. Afterwards, he joined the immunopathology laboratory in the Haematology Department at the Universi-ty Hospital of Salamanca, and started a PhD program under the supervision of Professor Jesús F. San Miguel. He received his PhD in 2011 from the Medical School of the Univer-sity of Salamanca, where he studied the cli-nical value of multiparameter flow cytometry

immunophenotyping of plasma cells in mul-tiple myeloma patients. Dr Paiva’s main area of work is on multiparameter flow cytometry evaluation of haematological malignancies. His main research interests focus on impro-ving the differential diagnosis, risk stratificati-on, and monitoring of patients with haemato-logical malignancies, particularly monoclonal gammopathies such as MGUS (Monoclonal Gammopathy of Undetermined Significan-ce), smouldering and symptomatic multiple myeloma, Waldenström’s macroglobulinae-mia, amyloidosis but also acute leukaemia’s and lymphoproliferative disorders. During the 2015 International Myeloma Workshop (IMW) he received the prestigious Bart Barlo-gie Young Investigator Award, which honours investigators under 40-year-old who have made major scientific contributions in terms of publications, funding received and prior awards or recognition. Dr Paiva is an author or co-author of several publications in peer reviewed journals.

BRUNOPAIVA

Universidad de NavarraPamplona, Spain

NGF for immune profiling, MRD assessment and detection of circulating plasma cellsFriday, February 1, 10:35 – 11:00

1. Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion, wherein tumor cells carry many of the genetic changes found in MM cells. Intraclonal heterogeneity is also esta-blished early during the MGUS phase.

2. The number of circulating tumor cells (CTCs) predicts risk of transformation in smoldering MM and survival in active MM.

3. CTCs are emerging as key players in the dissemination of MM.

4. Interactions of MGUS and SMM tumor cells with immune cells, bone cells, and others in the bone marrow niche may also be key regulators of malignant transformation.

5. Bone marrow cell immuno-profiling of the entire spectrum of these disorders may have broader implications beyond preven-tion of clinical malignancy or progressive disease after complete response (CR) to treatment in active MM.

6. I will show results, based on intensive treat-ment and MRD monitoring using NGF, unveil that achieving MRD-negativity may

overcome the poor prognosis of HR cyto-genetics. By contrast, persistent MRD sig-nificantly reduces PFS rates, particularly in patients with del(17p).

7. I will also show that immune profiling con-comitant to MRD monitoring may contribute to identify patients with poor, intermediate, and favorable outcomes.

8. I will present data suggesting that MM pati-ents with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and reco-very of B-cell production and homing, sug-gesting improved immune surveillance.

9. There is a clear unmet need to develop accurate immune monitoring to select pati-ents with both pre-malignant as well per-sistent MRD that could benefit from specific immunotherapy approaches.

10. The development of big datasets is a cri-tical step to bring next-generation immune monitoring from bench to bedside, and fos-ter precision immunotherapy in MM.

BRUNOPAIVA


Clinical Lecturer, The Institute of Cancer Re-search and Royal Marsden Hospital, London.

Charlotte received her degrees in pharma-cology and medicine from St John’s College, Cambridge University. She completed initial medical training in the East Anglian and North London deaneries before starting haemato-logy specialty training with an Academic Clini-cal Fellowship at the Royal Marsden Hospital and The Institute of Cancer Research, London. In 2016 she completed a Wellcome Trust fun-ded PhD Fellowship, undertaking laboratory research to identify novel epigenetic targets for myeloma therapy.

During her PhD Charlotte was awarded a ‘Women in Cancer Research Scholar Award’ from the American Association of Cancer Research. In addition to her laboratory stu-dies Charlotte is actively involved in several clinical trials including the large UK national study, Myeloma XI. She has published nume-rous peer-reviewed research papers and is pursuing her laboratory research interests alongside her clinical career, with a focus on therapeutic targets to improve outcomes for patients with high-risk myeloma.

CHARLOTTEPAWLYN

The Institute of Cancer ResearchLondon, United Kingdom

The role of bone marrow stroma in multiple myelomaFriday, February 1, 08:45 – 09:10

1. Multiple myeloma plasma cells exist as part of a complex ecosystem within the bone marrow stroma, which co-evolves along-side the myeloma cells.

2. The bone marrow stroma is a complex organ consisting of cellular and non-cellular compartments:

a. The cellular compartment comprises both haematopoietic and non-haema-topoietic cells including immune cells, endothelial cells, mesenchymal stromal cells, osteoblasts and osteoclasts. b. The non-cellular compartment com prises extracellular matrix and liquid milieu carrying cytokines, chemokines and growth factors.

3. Together these stromal compartments pro-vide the microenvironment that surrounds bone marrow plasma cells.

4. Within their niche normal long lived plasma cells engage with the microenvironment to facilitate keeping them out of cell cycle, mediating their long-term survival. Similar processes enable myeloma cell survival and may contribute to their oncogenic drive.

5. Interactions between the myeloma cell and its microenvironment are mediated by a number of mechanisms including direct ligand cell-cell interaction and secreted agents such as cytokines.

6. MM cells and their microenvironment col-lude to promote tumour cell growth with myeloma cells influencing their microenvi-ronment to promote their own growth at the expense of non-malignant haematopoietic cells.

7. Evolution of disease from MGUS to smoul-dering myeloma to myeloma is associated with a shift in the balance of immune sur-veillance leading to an immunosuppressive environment allowing the immune-escape of myeloma cells.

8. The complexity of microenvironment inter-actions and their wide ranging influences are important to consider when studying the biology of myeloma and designing models for testing new agents.

9. Targeting the microenvironment directly holds therapeutic potential.

CHARLOTTEPAWLYN


Leo Rasche, MD, attended medical school at the University of Würzburg in Germany and earned his MD in 2009, with the focus on experimental pathology, where he subsequently completed his residency in internal medicine and was a consulting specialist in internal medicine and hematology/oncology. Between 2016 and 2018 he has been a postdoctoral fellow at the Mye-loma Institute at the University of Arkansas for Medical Sciences in Little Rock, where he stu-died medical imaging, tumor genomics, tumor evolution, and immunotherapy approaches for treating multiple myeloma. In 2018 he was appo-inted an assistant professor of research at the University of Arkansas for Medical Sciences. In summer 2018, Dr. Rasche returned to Germany

where he serves as an attending physician on the myeloma service at the University hospital of Würzburg.

Dr. Rasche has published numerous articles in peer-reviewed journals such as Nature Commu-nications, Nature Reviews Clinical Oncology, Blood, and Leukemia. He presented his findings at national and international conferences, and serves as reviewer for prominent journals, inclu-ding Haematologica and the British Journal of Haematology.

Dr. Rasche holds membership with several pro-fessional organizations, including the Internatio-nal Myeloma Working Group (IMWG).

LEORASCHE

University Hospital WürzburgWürzburg, Germany

NGS in MM, clinical relevance and prospects for the future Friday, February 1, 09:10 – 09:35

1. Next Generation Sequencing (NGS), based on massively parallel DNA sequencing, all-ows for determining the order of nucleoti-des of an entire human genome within a few days.

2. In myeloma, NGS can be used to detect mutations with adverse prognostic impact, e.g. TP53 mutations. Recent studies have identified biallelic TP53 inactivation (“Dou-ble hit”) to be associated with ultra high-risk myeloma with a median survival of less than 2 years. There is an urgent need for clinical trials evaluating new concepts for these patients. Of note, this “Double Hit” group does not replace previous risk mar-kers identified by FISH or ISS but provides additional prognostic information.

3. Complex chromosomal aberrations and copy number alterations characterize mye-

loma. Thus, long-read sequencing techno-logies are more suitable to study myeloma genomes.

4. Minimal residual disease (MRD) status can be determined using sensitive tests based on NGS. However, spatial heterogeneity challenges these molecular tests as they rely on tumor samples usually collected from the iliac crest. As recently shown, the mutational profiles can be very different at other sites. The same holds true for the dis-tribution of MRD, and MRD tests may be false negative at the iliac crest site.

5. NGS sequencing technology remains a powerful discovery tool in tumor biology, e.g. single cell RNA sequencing brings the opportunity to analyze myeloma cells in their microenvironment.

LEORASCHE


Jesús San-Miguel, MD, PhD, is a professor of medicine-hematology and director of clinical and translational medicine at the University of Navarra in Spain. He served as director of the Hematology Department of the University Hos-pital of Salamanca in Spain, for over 22 years (1991-2013).

Dr San-Miguel has published over 800 original papers in international journals. He has made important contributions to myeloma cell biology in areas such as immunephenotyping, risk of progression from monoclonal gammopathy of undetermined significance or smouldering MM into active MM, and minimal residual disease, as well as, making important contributions in the area of therapeutics, including studies for new antimyeloma drugs at the preclinical and clinical levels, including proteasome inhibitors, immuno-modulatory drugs, and histone deacetylases.

He is currently President of the International Myeloma Society and member of the Advisory Board of the International Myeloma Foundation and the Multiple Myeloma Research Founda-tion. He has served as board councillor for the European Association, chairman of the Scien-tific Committee for the IXth Congress (2004), and president of the 15th European Hematology Association (EHA) Congress. He has been associate editor for Blood and Hematologica. He has received numerous awards, including the Waldenstöm Award, EBMT Lecture Award, Kyle Lifetime Achievement Award, Jose Carreras EHA Award, Ham-Wasserman Lecture Award, Rey Jaime I Award in Clinical Medicine, and the Spanish Prizes in both oncology and translatio-nal research.

JESÚSSAN-MIGUEL

Clínica Universidad de Navarra Pamplona, Spain

Keynote lecture: The roadmap to cure patients with multiple myeloma?Saturday, February 2, 08:30 – 09:00

1. The first reports of cure in multiple mye-loma (MM) were with allogeneic trans-plant, but this remains as an investigatio-nal approach for a very small fraction of patients.

2. In the era of chemotherapy with Autolo-gous stem cell transplant only 5-10% of MM patients remain in CR > 10 years and can be considered operationally cured. However, to consider MM a potentially curable disease the fraction of patients in cCR ( at 10y) should increase to 40-50%.

3. In most malignancies to achieve cure require to eradicate all malignant clones and this imply to integrate all active treat-ment tolls through induction, consolidation & maintenance.

4. To offer intensive therapies to high-risk patients and a gentle treatment to stan-dard risk patients is a wrong philosophical approach. If cure is the goal, the risk of undertreating low risk patients by conclu-ding they are in conventional CR may be a serious error.

5. In high risk patients experimental approa-ches should be investigated. Effective treat-ment may not be a matter of dose intensity, but of dose density.

6. A pre-requisite for cure is to achieve and maintain the best possible response early in the course of the disease.

7. Minimal residual disease (MRD) assess by next generation flow cytometry or sequen-cing ( with a sensitivity of 10-6) are the most sensitive biomarkers for long term survival a potentially cure.

8. CT-PET is complemamtary tool to evaluate MRD outside the BM.

9. To treat the disease early on. In most malig-nancies (lung, colon, prostate, breast …) early detection and intervention is associa-ted with a high cure rate. High risk smolde-ring myeloma are candidate for investiga-tional studies.

10. To achieve cure, MM should not be consi-dered a single entity, and treatment strate-gies should be adapted to the MM subtypes

JESÚSSAN-MIGUEL


Pieter Sonneveld is Professor of Hematology at the Erasmus MC Cancer Institute and the Erasmus University of Rotterdam, The Net-herlands. He received his medical degree from the Erasmus University Rotterdam and completed his PhD at the University of Leiden, The Netherlands, and received a Fogarty Fel-lowship at the National Cancer Institute in the United States for 2 years.

Professor Sonneveld is chair of the Dutch HOVON Myeloma Group. He was one of the founders of the European Myeloma Network (EMN) and is currently the chair. Within EMN, he organized a cooperative network for clinical trials, which has resulted in nine large Euro-pean Intergroup trials and scientific workshops for the standardization of diagnostic methods

in Europe. Within the European Hematology Association (EHA), Professor Sonneveld has been chosen President and he serves on the Fellowships & Grants Review Committee, is chair of the Scientific Working Group on ‘Multiple Myeloma’ and has been a reviewer for many years. He served on the scientific advisory boards of the International Myeloma Foundation (IMF), the International Myeloma Working Group, and the International Mye-loma Society, and has been a member of the Editorial Boards of Blood, Leukemia, Leuk-emia Research, Haematologica, and Annals of Haematology. Professor Sonneveld is the author of more than 400 scientific publications and several book chapters. In 2015 Professor Sonneveld received the Robert F. Kyle Life-time Achievement Award.

PIETERSONNEVELD

Erasmus University Medical CenterRotterdam, The Netherlands

How I treat high risk diseaseSaturday, February 2, 09:25 – 09:50

1. The definition of high-risk disease at diagnosis is based on clinical findings, disease related aspects and cytogenetic abnormalities.

2. High-risk cytogenetic abnormalities as determined by FISH include deletion 17p, t(4;14), t(14;16), t(14;20) and possibly add 1q.

3. High-risk clinical characteristics include ISS 3 (albumin, Beta-2-Microglobulin), elevated LDH.

4. High-risk clinical conditions include high age, frailty, renal impairment, severe concomitant disease.

5. The above characteristics are frequently used for selection of patients in clinical trials.

6. More recently, molecular abberations (mutations, pathways, gene expression signatures) have been recognised as important markers of high-risk disease.

7. Clinical checkpoints for poor-risk disease in clinical trials include not achieving a significant response (CR, VGPR) or MRD negative status.

8. The therapeutic approach to high-risk disease is under discussion and varies with the access to novel agents and intensive treatment.

PIETERSONNEVELD


Evangelos Terpos, MD, PhD is a Professor of Hematology in the Department of Clinical Therapeutics of the National & Kapodistrian University of Athens, School of Medicine, Athens, Greece.

His main research interest is the biology of plasma cell dyscrasias and especially the bio-logy of bone disease in multiple myeloma (MM). In more than 450 papers in peer-reviewed jour-nals, Dr Terpos has reported the significant role of RANKL and osteoprotegerin axis, CCL-3 (MIP-1alpha), Wnt and TGF-beta signaling in myeloma bone disease and myeloma cell growth. He has studied the predictive value of markers of bone remodeling and osteoclast function in myeloma progression and patients’ survival. He has evaluated the effect of bisphos-phonates and different anti-myeloma therapies including ASCT, IMiDs- and bortezomib-based regimens on bone metabolism. He has studied the biology and prevalence of osteonecrosis of the jaw in myeloma patients who receive bisphosphonates. Dr Terpos also works on the role of modern imaging (including whole-body low-dose CT and MRI) for MM, of angiogenesis in MM and Waldenstrom’s Macroglobulinemia, and of renal impairment in MM. In the clinical

research era, Dr Terpos participates in seve-ral important clinical trials with novel agents (pomalidomide, carfilzomib, ixazomib, daratu-mumab, elotuzumab, isatuximab, anti-BCMA, etc) in the field of multiple myeloma.

Dr Terpos is also interested in the biology and management of bone disease in other hemato-logy disorders, including hemoglobinopathies, hemophilia and histiocytosis.

Dr Terpos is co-chairing the Bone Subgroup of the International Myeloma Working Group and the Guideline Subgroup of the European Myeloma Network. He is member of the Board of the Greek Society of Hematology since 2015 and Vice-President of this Society for 2016-2018. Dr Terpos has given lectures at ASH, ASCO & EHA meetings, International Myeloma Workshops, International Mee-tings on Cancer-Induced Bone Disease and in several national meetings. He is reviewer of scientific papers in more than 50 medical journals and has reviewed abstracts for ASH, EHA & EBMT meetings. He is Associate Edi-tor of HemaSphere (official journal of EHA) for Myeloma and member of the editorial board of Haematologica.

EVANGELOSTERPOS

General Hospital of AthensAthens, Greece

Pathophysiology and Management of myeloma bone disease Workshop: Friday, February 1, 11:25 – 12:15 and 15:55 – 16:45

1. Osteolytic bone disease is the most com-mon complication of multiple myeloma. Bisphosphonate remain the cornerstone of the management of myeloma-related bone disease.

2. All myeloma patients with normal renal function and osteolytic disease at dia-gnosis should be treated with zoledronic acid (preferably) or pamidronate, intrave-nously, in addition to specific anti-myeloma therapy. Symptomatic patients, without bone disease assessed by conventional radiography, should also receive zoledro-nic acid, but its advantage is not clear for patients with no bone involvement on MRI or PET/CT. In asymptomatic MM, bisphos-phonates are not recommended.

3. Zoledronic acid should be given for more than two years only in patients with active MM. For patients who have achieved CR or VGPR, 12-24 months of therapy with bisphosphonates should be adequate. At relapse, bisphosphonates have to be rei-nitiated.

4. In cases of osteonecrosis of the jaw (ONJ), bisphosphonates should be discontinued and can be re-administered if ONJ has healed.

5. In patients with CrCl <30 mL/min bisphos-phonates are not recommended. Denosu-mab is a logical approach for these pati-ents, although there are limited data in the field.

6. In the largest placebo-controlled trial for myeloma patients to-date, denosumab was compared to zoledronic acid. Alt-hough, there was no difference regarding time to first skeletal-related event (SRE), a landmark analysis at 15 months showed a superiority of denosumab in terms of SREs. Furthermore, denosumab showed a better renal safety profile along with an advantage in progression-free survival, mainly for patients who received an autolo-gous transplant and for patients who recei-ved a proteasome inhibitor-based regimen as frontline treatment. Thus, denosumab is another standard of care for myeloma-re-lated bone disease.

7. Denosumab has to be given continuously. Discontinuation of denosumab is challen-ging as there are no data on how to stop denosumab in myeloma patients.

8. Low-dose radiation therapy (up to 30 Gy) can be used as palliative treatment for uncontrolled pain, for impending patholo-gic fracture, or impending spinal cord com-pression.

9. Balloon kyphoplasty should be considered for symptomatic vertebral compression fractures.

10. Surgery is recommended for long-bone fractures, bony compression of the spinal cord, or vertebral column instability.

EVANGELOSTERPOS


Niels van de Donk, MD, PhD is a hematolo-gist at the VU University Medical Center in Amsterdam, The Netherlands. He completed his medical degree at the University Medical Center Utrecht. Prior to this he had obtained a Bachelor’s degree in Pharmacy and a Mas-ter’s degree from the University Medical Cen-ter Utrecht, where he also completed his PhD studies, which were focused on new treatment strategies for multiple myeloma by targeting Bcl-2 and the mevalonate pathway.

He trained as an internist at the University Me-dical Center Utrecht, where he also pursued his specialization in hematology. Following a fellowship at the Jerome Lipper Multiple Mye-loma Center, Dana-Farber Cancer Institute in Boston, USA, he became a hematologist in

the Department of Hematology at the Univer-sity Medical Center Utrecht before assuming his current post at the VU University Medical Center in Amsterdam.

Dr. van de Donk’s special interest is the treatment of patients with multiple myeloma and he is involved in translational research towards finding new targets for therapy with a focus on immune therapy. He is author or co-author of a number of books and many papers published in peer-reviewed journals and a reviewer for several journals including Blood, Leukemia, and Haematologica, as well as associate editor of the Netherlands Journal of Hematology. He is also secretary of the HOVON multiple myeloma working party.

NIELSVAN DE DONK

VU University Medical CenterAmsterdam, The Netherlands

Impact of monoclonal and bispecific antibodies in myeloma therapy today and tomorrow Saturday, February 2, 09:00 – 09:25

1. Monoclonal and bispecific antibodies are transforming multiple myeloma treatment.

2. CD38-targeting antibodies have potent single agent activity by inducing clas-sic Fc receptor-mediated activities such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cyto-toxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In addition, CD38 antibodies have immunomodula-tory effects by eliminating CD38-positive regulatory T cells, regulatory B cells, and myeloid-derived suppressor cells. CD38 antibodies synergize with lenalidomide, pomalidomide, and proteasome inhibi-tors.

3. SLAMF7-targeting agents induce ADCC, and also activate NK cells. SLAMF7-tar-geting agents have no marked single agent activity, but combined with standard of care regimens lenalidomide-dexamet-

hasone and bortezomib-dexamethasone results in improved outcome as compared to standard of care alone.

4. Both CD38 antibodies and SLAMF7-targe-ting antibodies are incorporated in first-line regimens in both transplant eligible and transplant-ineligible patients; early results will be discussed during the meeting.

5. These antibodies are also promising agents for high-risk SMM patients.

6. New management aspects concerning these monoclonal antibodies include: 1) response evaluation, 2) infusion reac-tions; and 3) blood transfusion typing.

7. Bispecific antibodies that redirect T-cells to MM cells have shown promising results in preclinical models. In addition, early results from clinical trials also show marked acti-vity of bispecific antibodies that redirect T-cells to BCMA-expressing MM cells.

NIELSVAN DE DONK


Elena Zamagni MD, PHD, is Assistant Profes-sor of Hematology at the University of Bolo-gna, Italy. She received her medical degree from University of Bologna, where she also served her residency in haematology. She got PHD in Clinical Hematology at the University of Bologna in May 2005.

Her research interests include areas related to multiple myeloma, in particular on the role of high dose therapy with stem cell support , of prognostic factors and of imaging techniques.

She has published over 90 papers in peer-re-viewed journals, mainly in the field of plasma

cell dyscrasia. She has contributed to the educational session of the Italian Society of Haematology. She is an active member of the board of the GIMEMA myeloma working party and she has cooperated in the Scienti-fic secretary and as principal investigator in several national randomized trials in multiple myeloma. She is a member of the Italian So-ciety of Haematology and of the International Myeloma Working Group. She is serving on the EHA’s Scientific Program Committee since 2017.

ELENAZAMAGNI

Seragnoli Institute of HematologyBologna, Italy

Imaging in myeloma bone diseaseFriday, February 1, 13:15 – 13:40

1. Novel imaging techniques are nowadays recommended both at diagnosis and after the end of treatment in MM. (IMWG New diagnostic criteria, Rajkumar V, Lancet Oncology 2014)

2. Whole-Body Low-Dose Computed Tomo-graphy (WBLDCT) is superior to conven-tional radiography for the detection of osteolytic lesions and it has replaced it in the work-up of myeloma patients. The CT part of PET/CT can be considered as a valid alternative when available.

3. Magnetic Resonance Imaging (MRI) is the best imaging method for the depic-tion of marrow infiltration by myeloma cells.

4. WB-MRI (or MRI of the spine and pelvis if WB-MRI is not available) should be per-formed in all patients with no lytic lesions at diagnosis for the exclusion of active myeloma. (IMWG New diagnostic crite-ria, Rajkumar V, Lancet Oncology 2014)

5. Functional imaging techniques are nowa-days required to evaluate minimal residual disease (MRD) after the end of treatment. (IMWG New response criteria, Kumar S, Lancet Oncology 2016)

6. FDG PET/CT is the best imaging technique for evaluating and monitoring response to therapy outside the BM and is recommen-ded by the IMWG. (Cavo M, Lancet Onco-logy 2017)

7. PET/CT has an independent prognostic value both at diagnosis and after treatment.

8. Functional whole-body MRI techniques (dynamic contrast enhanced, DCE and dif-fusion weighted imaging, DWI) seem pro-mising for response evaluation, but need further studies.

9. Standardization of PET/CT is on-going. (Zamagni, Blood 2018 abs)

10. A prospective comparison between PET/CT and DWI- MRI for the evaluation of MRD is desirable.

ELENAZAMAGNI

19th European Multiple Myeloma Academy | February 1-2, 2019 | Vienna, Austria 56

This event is supported by unrestricted educational grants from:

AbbVie: Bronze Sponsor

Celgene: Platinum Sponsor TAKEDA: Platinum Sponsor AMGEN: Gold Sponsor

Janssen: Silver Sponsor

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