Seminars in Hematological OncologyThirteenth International Educational Forum

Organizing chairman: Professor Aaron Polliack

T u e s d a y 2 4 t h , A p r i l 2 0 1 8

Under the auspices of theIsraeli Society of Hematologyand Blood Transfusions

D a n i e l H o t e l , H e r z l i a , I s r a e l

Dear colleagues and friends,

The first International Educational Forum - Seminars

in Hematological Oncology was held in April 2006.

Since then, it has become an established annual

event on the Hematological Oncology calendar of

the Israeli Society of Hematology every April. This

year we meet once again in Herzlia for the 13th

annual forum with an exciting international faculty

containing enthusiastic and talented speakers.

These include most of the permanent core faculty,

returning guest speakers and some new participants,

all recognized international leaders in their fields.

As in the past, they have rearranged their busy

committments and given us priority. Once again, we

welcome them warmly and thank them for accepting

this invitation so promptly and without hesitation.

Our friends and colleagues, Ayalew Tefferi, Morie Gertz and Martin Tallman have come to all of

these meetings since 2006. They are basically

the established core of the faculty and are here

again with the same enthusiasm and committment.

The same for Michael Hallek, Andreas Engert, Ola Landgren, Daniel Mertens, Gilles Salles, Wyndham Wilson and Tom Witzig who return yet

again. We welcome Andrea Bacigalupo, Florian Kuchenbauer and Akiko Shimamura for the first

time and sincerely hope they enjoy their time here

and will want to return for future visits.

As always, this event would not have been possible

without the help provided by our different sponsors,

the positive attitude of our international guest faculty

and the consistent strong support of the Society’s

executive committee. We are confident that this

will once again be a stimulating and successful

meeting as in previous years.

Let me thank all participants for coming from near

and far and extend special warm greetings to our

guests.

Welcome to all and please enjoy this special day.

Organizing Chairman: Professor Aaron Polliack

Professor Andrea Bacigalupo is currently Head of the Hematology Department and Transplant Unit at Policlinico Gemelli, Catholic University, in Rome, Italy. He has been involved in stem cell transplants since 1976, and in the European Group for Blood and Marrow Transplants (EBMT) since 1977. Prior to moving to Rome, Andrea served as the Head of the Division of Hematology and Stem Cell Transplants, at Ospedale San Martino, Genoa, Italy during 1989-2014. He has conducted several prospective clinical trials dealing with aplastic anemia and in patients undergoing allogeneic transplants: in particular he has been the principal investigator of nine prospective randomized studies in the field of graft versus host disease (GvHD). His main interests are bone marrow failure, GvHD and related complications, and graft versus leukemia reactions. Professor Bacigalupo has also been

Andrea Bacigalupo

interested in CMV and EBV infections, looking at early diagnosis and prospective studies on prophylaxis and pre-emptive therapy. Andrea has served on the board of EBMT for many years, as EBMT secretary, chairperson of the Aplastic Anemia Working Party and then as president for the 1998-2002 term. He was also president of the Italian Group of Bone Marrow Transplantation (GITMO) during 2002-2005 and has served on the Regimen Related Toxicity Working Group of the Center for International Blood and Marrow Transplant Research (CIBMTR). He been a member of the Italian Council of the Ministry of Health during 2001-2010). Professor Bacigalupo is also associate editor of the journal Bone Marrow Transplantation and Biology of Blood and Marrow Transplantation and is on the Board of Haematologica and the Journal of Clinical Oncology.

Andreas Engert

Since the year 2000 Andreas Engert is Professor of Medicine and Hemato-Oncology at the University Hospital of Cologne, Germany and Vice-Director of the Department of Medicine, Oncology and Hematology at the University Hospital of Cologne, Germany. He served first as Secretary of the German Hodgkin Study Group for seven years during 1999- 2006 and is now director and chairman of this group for the past 10 years since 2007. Professor Engert was also co-ordinating editor of the Cochrane Hematological malignancies group for 12 years during 2000- 2012. Andreas received his MD in 1985 from Hannover University, and since 1986 has been at the University of Cologne. His initial research interests were in the field of the development of novel recombinant proteins - immunotoxins and bi-specific antibodies for use in cancer immunotherapy and targeting of tumor blood vessels. During 1988- 1990 he had worked specifically on antibody- based immunotherapy and

in clinical and tumor immunology at the Royal Free Hospital in London before returning permanently to the University Hospital in Cologne in 1991 to head the Laboratory for Immunotherapy. From as early as 1988 , Andreas has been a central figure in many important clinical trials related to lymphomas particularly Hodgkin Lymphoma which he continues to lead until now. For many years now, he has been the hardworking major organizer of the largest and most important European and international meeting on Hodgkin lymphoma held in Cologne, every three years.Andreas is very active in the framework of the European Hematology Association (EHA) and is Editor in Chief of their new journal Hemasphere. He is also Scientific Director in Lymphoma of the European School of Oncology.Professor Engert has received achievement awards from the German Society of Hematology & Oncology for his studies on Hodgkin lymphoma.

Dr. Gertz is Professor of the Art of Medicine and Chair of the Department of Internal Medicine, at the Mayo Clinic in Rochester, Minnesota. He is a Master of the American College of Physicians. His undergraduate degree was awarded with highest distinction from Northwestern University.Dr. Gertz received his medical degree cum laude from Loyola Medical School in Maywood, Illinois and was elected to Alpha Omega Alpha the medical honor society. He completed a 3-year medical residency at Rush Presbyterian St. Luke’s Hospital in Chicago, Illinois, and was voted Resident of the Year for 2 of those years. Dr. Gertz completed training in hematology and oncology at the Mayo Clinic before doing amyloidosis research at the Thorndike Laboratory at the Boston City Hospital Foundation. He has served as President of the Mayo Rochester Officers & Councilors

Morie Gertz

and was awarded the Mayo Distinguished Clinician Award for his contributions to patient care. He also received the Robert Kyle award from the International Society of Waldenstrom’s Macroglobulinemia. Prof. Gertz previously served on the Mayo Clinic Rochester Executive Board, was Chair of The Personnel Committee and was also appointed as the first Co-chair of the National Cancer Institute Myeloma Steering Committee. He was the first treasurer of the International Society of Amyloidosis and currently is treasurer of the International Myeloma Society. Morie has authored many publications and book chapters and is regarded as one of the most talented and devoted teachers at the Mayo Clinic. He is in great demand as an international speaker and his reputation and expertise in plasma cell dyscrasias are well recognized worldwide.

Professor Michael Hallek received most of his training during 1985-1995 in pharmacology, internal medicine, hematology and medical oncology at the University of Munich in Germany. From 1990-1992 he worked as a Research associate at the Dana Farber Cancer Institute, Harvard Medical School in Boston and returned to Munich in 1992. Dr. Hallek was appointed Professor of Medicine at Munich in 1999 and then Director of the Department of Medicine in 2003. He was also Head of the Gene Therapy Program there from 1994 until 2005. In 2006 he moved to Cologne to take up the position of Director of the Center for Integrated Oncology and the Comprehensive Cancer Center of the Universities of Cologne and Bonn. The latter is one of the four Centers of Excellence in Oncology in Germany. At the same time Professor Hallek also served as President of the German Society for Gene Therapy from 2002 to 2006.

Michaek Hallek

In 1996 he founded the German CLL Study Group- GCLLSG, which is today the largest multicentreCLL group in the world. He still remains the group’s active organizing chairman and central driving force. The GCLLSG continues to run successful multicentre randomized clinical trials and has made major contributions to the concept of modern therapy for CLL, as a direct result of his careful planning of these large clinical trials. Professor Hallek is also a member of the scientific committee of the International Workshop on CLL, chairman of the German Competence Network on Lymphoma and serves on the advisory board of a number of different national and international committees and institutes. He has written many original papers and reviews mostly relating to the biology and treatment of CLL, which continue to be published in the leading journals in the field of Hematological Oncology. He remains a world leader in CLL today.

Florian Kuchenbauer is an attending physician for the stem cell transplant unit in the department of Haematology/ Oncology at the University Hospital Ulm in Germany. He received his MD at the Medical School at Munich University and completed post graduate training at the Universities of Munich and Ulm. Dr Kuchenbauer earned his PhD in the Experimental Medicine Program of the Cancer Research Center at the University of British Columbia and Terry Fox Laboratory in Vancouver, Canada.After returning to Germany in 2009, Florian successfully continued his work on non-coding RNAs and started a research group funded by the German Cancer Society and German Research Association (DFG) in Ulm. His studies, which applied next-generation sequencing to miRNAs in leukemia cells for the first time, have contributed much to the miRNA field, and have opened new research avenues for “isomiRs”. Furthermore, his work highlighted

Florian Kuchenbauer

the role of several miRNAs in myelodysplastic syndromes and acute myeloid leukemia as well as normal hematopoiesis, thereby providing functional insight as well as valuable resources for future research programs. Building on his initial studies, Florian’s most recent research interest has shifted towards the possible clinical application of miRNAs in the treatment of hematological malignancies.In addition, he is particularly interested in improving the clinical outcome of allogeneic stem cell transplantation by exploring the role and therapeutic use of non-coding RNAs in modulating the stem cell niche.Dr. Kuchenbauer was initially a young investigator and group leader of the project “Experimental models and clinical translation in leukemia“ in the bone marrow transplantation unit in Ulm.He now serves as deputy head of this Unit at the University of Ulm.

Ola Landgren

Since 2014 Ola Landgren is Chief Attending Physician of the Myeloma Service in the Department of Medicine at the Memorial Sloan Kettering Cancer Center and Professor of Medicine at Weil Cornell Medical College in New York. Before this and during the period 2004 - 2014, he was Senior Investigator at the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda. During 2009 - 2014 he lead the Multiple Myeloma Section at the NCI/NIH and also served as the Chairman of the Scientific Review Committee at the Medical Oncology Branch. Ola received his MD in 1995 and his PhD from the Karolinska Institute, Stockholm, Sweden and led clinical research on lymphoproliferative malignancies until joining the NIH /NCI in 2004.Dr. Landgren is one of the younger leading international physician-scientists with research

focus on multiple myeloma and its precursor diseases. Ola has planned several landmark studies focusing on MGUS and progression patterns into multiple myeloma. In his first prospective study, he showed that all myeloma patients are preceded by an earlier MGUS stage. His studies on racial disparity patterns for MGUS and multiple myeloma among African-Americans and whites, and familial aggregation patterns for these malignancies in Scandinavia, have provided novel insights supporting a role for genetic and immune-related factors in myelomagenesis. Ola is the Principal Investigator for several treatment studies focusing on multiple myeloma and has been involved in some of the most active treatment programs designed for early myeloma. He has an extensive publication track-record in leading peer-reviewed journals.

Daniel Mertens trained as a biochemist in the Institute for Physiological Chemistry in Tübingen and during 1996-1999 continued in organic biochemistry and Developmental Genetics and Biology. He then spent time at the DKFZ-the German Cancer Research Center in Heidelberg with the world renowned Professor Harald zur Hausen, working on aspects of the cell cycle. He completed his PhD (cum laude) and thereafter,continued postdoctoral research at the German Cancer Research Center working on tumor suppressor genes particularly chromosomal band 12q14.3 in chronic lymphocytic leukemia (CLL). His translational research on this complex locus shed light on an intriguing epigenetic regulatory network which revealed new data on miRNAs - miR15 and miR16. In 2006 Dr. Mertens established a second research group at the University Hospital in Ulm in the department headed by Professor Hartmut Döhner.

Daniel and his team, have contributed much to the understanding of how primary CLL cells rapidly undergo apoptosis when cultured in-vitro, and how CLL cell death can be prevented by co-culture with bone-marrow derived stromal cells. These studies indicate that this microenvironmental interaction would probably be an ideal target for therapy in leukemia. Dr. Mertens has already added much to our understanding of the mechanisms of leukemogenesis and will no doubt continue to do so in the future. He is currently group leader at the German Cancer Research Center in Heidelberg and also heads another research group at the University Hospital of Ulm which continues to focus on microenvironmental signal transduction.He now leads the co-operation Unit dealing with ”mechanisms of leukemogenesis” and the project of “overcoming resistance in leukemia” at both the above centers.

Daniel Mertens

Gilles Salles is Professor in the Department of Haematology at the Centre Hospitalier Lyon-Sud,Lyon, France, and Head of the Research Unit“Clinical and Experimental models of lymphomagenesis” at the University of Lyon in France. He completed all his early and postgraduate training in Lyon France and also spent two years as a senior research fellow at the Dana Farber Cancer Institute and Harvard Medical School in Boston.After his return to Lyon he served as Chairman of the Scientific Committee of the GELA (Groupe d’Etude des Lymphomes de l’Adulte) until 2007 and is currently president of the Lysa (Lymphoma Study Association) cooperative group.

Professor Salles has always been especially interested in the clinical and biological aspects of malignant lymphoma and the major focus of hiswork has included the description and validation of prognostic factors, as well as clinical trials in indolent lymphoma. Throughout the years he has also been involved as a coordinator or co-investigator in many national and international clinical trials particularly in lymphoma and has published much on these topics.Dr. Salles is an active member of the American Society of Hematology, the American Society of Clinical Oncology and European Hematology Association.

Gilles Salles

Dr. Akiko Shimamura is the Director of the Bone Marrow Failure and Myelodysplastic Syndrome Program at the Dana Farber/Boston Children’s Cancer and Blood Disorders Center. She is Associate Professor of Pediatrics at Harvard Medical School in Boston, Massachusetts. Dr. Shimamura received her undergraduate degree in biochemistry at Princeton University and her MD and PhD in biology at the University of Rochester. She completed her initial training in pediatrics at Johns Hopkins Medical Center Baltimore, followed by a fellowship period in Hematology/Oncology at Dana Farber Cancer Institute and Boston Children’s Hospital. She joined the faculty at Harvard Medical School until 2007, when she moved to Seattle Children’s Hospital and the Fred Hutchinson Cancer Research Center, as to Professor of Pediatrics and full Member. In 2015 she returned to Harvard and holds the Chair in Hematology - Oncology. Dr. Shimamura has a long-standing interest in the field of bone marrow failure and currently directs laboratory and clinical

studies of genetic bone marrow failure and leukemia predisposition syndromes. Dr. Shimamura founded and directs the North American Shwachman Diamond Syndrome Registry to elucidate the natural history, clinical outcomes, and molecular pathophysiology of Shwachman Diamond Syndrome aiming to improve treatment. Akiko Shimamura serves on the Executive Committee of the North American Pediatric Aplastic Anemia Consortium, a working group of over 30 pediatric hematology centers.Her recent research has focused on identification of genes causing bone marrow failure and leukemia predisposition. Her work has informed evidence-based integration of genomic testing into diagnostic algorithms for these disorders. Dr. Shimamura served as scientific co-chair of the annual American Society of Hematology meeting in 2015 and chaired the Germline Genomics subcommittee of the ASH Precision Medicine Task Force. She serves on the medical and scientific advisory boards of several foundations including the MDS Foundation and the Shwachman Diamond Syndrome Foundation.

Akiko Shimamura

Professor Martin Tallman is now chief of the Leukemia Service at the Memorial Sloan KetteringCancer Center in New York since early 2010.He is also Professor of Medicine at the Weil Cornell Medical College New York. Before moving to New York Martin was Professor of Medicine for over 20 years at the Northwestern University Feinberg School of Medicine and Co-Director of the Hematologic Malignancy Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois. He is currently chairman of the Leukemia Committee of the Eastern Cooperative Oncology Group.Dr. Tallman received his MD at the Chicago Medical School, completed his residency at the Medical Center at Northwestern University, and his fellowship in Hematology-Oncology at the

Martin Tallman

University of Washington the Fred Hutchinson Cancer Research Center in Seattle, Washington.Dr. Tallman is a member of numerous committees of national, regional, and international societies involved in the study and treatment of cancer. He also serves on the AML, CML and MDS Committees of the National Comprehensive Cancer Network (NCCN).During his career he has also contributed a largebody of work to the literature addressing the diagnosis, biology, and treatment of acute leukemia and other hematologic malignancies. Professor Tallman serves as an Associate Editor of Blood and is also on the editorial boards of a variety of scientific journals. He is a frequently invited speaker at meetings in the USA and other countries.

Professor Ayalew Tefferi was born in Ethiopia and emigrated to the USA in 1982 after completing his medical education at the University of Athens in Greece. Dr. Tefferi received his Hematology training at the Mayo Clinic in Rochester, MN, USA before joining the staff at the Mayo Clinic College of Medicine, Division of Hematology.Since 2001 he has been a full professor at the Mayo Medical Center and Mayo Medical School.Dr. Tefferi spends the majority of his time in direct patient care and his clinical and laboratory interests focus on chronic myeloproliferative disorders, myelodysplastic syndrome, chronic myeloid leukemia, hypereosinophilic syndrome, and systemic mast cell disease. His academic and research achievements are impressive and include hundreds of publications including books, book chapters, reviews, editorials, and original articles. In addition, Dr. Tefferi serves

Ayalew Tefferi

as an associate editor for both the Mayo Clinic Proceedings, the European Journal ofHematology and the American Journal of Hematology as well as being on the editorial board for Blood and several other Hemato-Oncology journals. He has given many national and international invited lectures and serves as faculty for the annual Hematology and Oncology Board review courses at George Washington University in Washington DC, Harvard in Boston, and MD Anderson Cancer Center in Houston.Prof. Tefferi is regarded as an outstanding teacher and has been the recipient of many “teacher of the year” awards at the Mayo Clinic, as well as the Dean’s Recognition award and the Distinguished Mayo Medical School Service Award.In 2016 he received the ASH Henry Stratton Medal for his life time work in Hematology and for mentoring.

Dr. Wilson obtained his, MD and PhD in 1981 and completed his medical residency at Stanford University, in California. Following a fellowship in Medical Oncology at the National Cancer Institute, NIH in Bethesda, Maryland in 1988,Dr. Wilson joined the faculty of the NCI as the Special Assistant to the Director in the Division of Cancer Treatment, and later as a principal investigator. He was first Head of the Lymphoma Clinic of the Division of Sciences at the NCI and also of Experimental Transplantation and Immunology. Dr. Wilson is now the Chief of the Hematological Malignancies Therapeutics Section, Metabolism Branch, Cancer Research Center at the NCI. He has received the Merit award of the NIH in 1994, was Teacher of the Year of the Medicine Branch in 1997 and received the Director’s award of the NIH in 1997 and the NCI in 2010. He has chaired the ASH scientific committee on Lymphoid Neoplasia in 2009-2010 and now serves as Chairman of the important and powerful Oncologic Drug Review

Wyndham Wilson

Committee of the FDA. Dr. Wilson’s interests are in the study of the pathobiology and treatment of lymphoid malignancies and he directs phase I, II and III translational studies. His work has focused on the development of new therapeutic strategies including novel targeted therapies using pharmacodynamic approaches. He has a special interest in the treatment of diffuse large B-cell lymphoma and EBV-driven and HIV associated lymphoproliferative disorders. Wyndham has developed novel treatments for subtypes of large cell lymphoma including mantle cell lymphoma, Burkitt lymphoma, and lymphomatoid granulomatosis. Primary mediastinal B cell lymphoma and the grey zone lymphomas have also been a special field of interest for him in recent years.Dr. Wilson has received numerous awards for his work and has multiple collaborations with other laboratory groups at the NIH including Dr’s Lou Staudt, Elaine Jaffe and Ira Pastan at the NCI.

Thomas Witzig

Thomas Witzig, is Professor of Medicine and consultant in the Division of Hematology at Mayo Clinic. He received his MD at Illinois University College of Medicine and continued with clinical hematology and oncology at Mayo Clinic until today . Dr. Witzig has received a number of awards during his career, including the Department of Medicine Outstanding Investigator at MayoClinic, Medical Honoree at the Lymphoma Research Foundation, and the Alumni Achievement Award at Illinois State University. In 2013, he was Mayo Teacher of the Year for the Divisions of Hematology and Oncology. Tom is active in ASH, ASCO, American Association for Cancer Research, American Medical Association, ECOG and the American College of Physicians. He also served as editor for Mayo Clinic Proceedings and on the Clinical Lymphoma Editorial Board. Tom is an excellent teacher

and mentor and has given numerous invited international presentations. Apart from his many publications he has also co-authored books and book chapters in Hematology and is well recognized internationally.Dr. Witzig’s clinical practice interests focus on the therapy of lymphomas and CLL, multiple myeloma, amyloidosis, and macroglobulinemia, as well as autoimmune immunological disorders. His research concentrates on new treatments for these diseases and his current focus is on agents that disrupt signal transduction pathways in cancer cells. Tom has been a leader in the development of radio-immunotherapy, mTOR inhibitors, and lenalidomide for the treatment of lymphoma. As a principal investigator and project leader, his research has been mostly funded by the NIH and NCI as well as the National Center for Complementary and Alternative Medicine.

Programme:

07:30-08:25 Registration and reception

08:25-08:35 Welcome and introduction

08:35 - 10:30 SESSION I

08:35-09:00 Myeloproliferative neoplasms: 2018 updates Ayalew Tefferi Mayo Clinic Rochester, Minnesota, USA

09:00-09:25 Shifting paradigms in the treatment of acute myeloblastic leukemia

Martin Tallman Memorial Sloan Kettering Cancer

Center, Cornell Medical College, New York, USA

09:25-09:50 Bone marrow failure, myelodysplasia and leukemia predisposition

Akiko Shimamura Boston Children׳ s Cancer Center, Boston, Massachusetts, USA

09:50-10:15 Prognostic impact of non- coding RNAs on outcome in leukemia

Florian Kuchenbauer University of Ulm Ulm, Germany

10:15-10:30 Questions

10:30-11:00 Coffee

11:00-13:00 SESSION II

11:00-11:25 Haploidentical transplants: Here to stay Andrea Bacigalupo Policlinico Gemelli Catholic University Rome, Italy

11:25-11:50 Hodgkin Lymphoma - 2018 What is agreed and what is still an

issue Andreas Engert University Hospital of Cologne University of Cologne Cologne, Germany

11:50-12:15 Follicular lymphoma: the treatment paradigm Gilles Salles Centre Hospitalier Lyon - Sud University of Lyon Lyon, France

12:15-12:40 Double hit lymphomas - pathogenesis and treatment options Thomas Witzig Mayo Clinic Rochester, Minnesota, USA

12:40-13:00 Questions

13:00-14:00 Lunch

14:00-15:55 SESSION III

14:00-14:25 Genomically inspired treatments for lymphoma

Wyndham Wilson National Cancer Institute, NIH Bethesda, Maryland, USA

14:25-14:50 Chronic lymphocytic leukemia: novel concepts moving towards

control of minimal residual disease Michael Hallek Comprehensive Cancer Center Universities of Cologne & Bonn Cologne, Germany

14:50-15:15 How genetic and epigenetic aberrations impact on biology and resistance of chronic lymphocytic leukemia

Daniel Mertens University of Ulm and German Cancer Research Center Heidelberg, Germany

15:15-15:30 Questions

15:30-15:50 Coffee

15:50-17:25 SESSION IV

15:50-16:15 Waldenstrom’s macroglobulinemia: diagnosis, prognosis and therapy 2018

Morie Gertz Mayo Clinic Rochester, Minnesota, USA

16:15-16:40 Is clinical staging and measuring disease burden still relevant in myeloma care?

Ola Landgren Memorial Sloan Kettering Cancer Center Cornell Medical College New York, USA

16:40-16:50 Questions

16:50-17:20 Debate on multiple myeloma Morie Gertz & Ola Landgren Continuous therapy vs fixed duration of

therapy im myeloma maintenance

17:20-17:25 Closing comments

THANKS and APPRECIATION to the following sponsors:

RocheNeopharmJanssen

BMS

NovartisMedisonSanofiAbbvieTakedaAstellas