The evolving role of alkylating agents in multiple myeloma; from the past and present to next generation peptide drug conjugates
Dr. Paul Richardson, RJ Corman Professor of Medicine, Harvard Medical School
Discussion Dr. María-Victoria Mateos, Associate Professor of Medicine at the University of Salamanca, Spain
Dr. Pieter Sonneveld, Professor of Hematology at Erasmus MC and Erasmus University Rotterdam, Netherlands
Dr. Paul G. Richardson
After certification in Internal Medicine, Hematology and Medical Oncology, as well as working in Cancer Pharmacology from 1994 onwards at Dana-Farber Cancer Institute (DFCI), Dr. Paul Richardson joined the Jerome Lipper Myeloma Center in 1999, was appointed Clinical Director in 2001, and led the development of several first-generation novel drugs including bortezomib, lenalidomide and pomalidomide for the treatment of multiple myeloma. Subsequent studies focused on next generation novel drugs including panobinostat and second-generation proteasome inhibitors including ixazomib. More recently, his clinical innovations have been in the development of the breakthrough monoclonal antibodies elotuzumab and daratumumab for the treatment of both untreated and relapsed myeloma, as well as isatuximab and more broadly, antibody drug conjugates including belantamab mafodotin, as well as other immunotherapeutic strategies. In addition to these agents, he has contributed to the development of melflufen, a novel peptide drug conjugate and the first-in-class small molecule inhibitor selinexor, which targets XPO-1, a key nuclear export protein, as well as first-in-human studies of potent cereblon E3 ligase modulators (so called CELMoDs) for the treatment of relapsed and refractory myeloma.
Over the last decade, his major effort has been focused on the development of lenalidomide, bortezomib and dexamethasone (so-called RVD), including its incorporation as part of the Intergroup Francophone Myelome (IFM)/DFCI clinical trials in newly diagnosed patients eligible for stem cell transplant treated with RVDand the landmark DETERMINATION study in the USA. This regimen has generated an unprecedented response rate, leading to its adoption in this international study, as well as others in the United States and across the globe. This particular trial incorporates genomic and proteomic evaluation to establish a future platform for tailored therapy and the optimal positioning of stem cell transplant, with results reported in 2022 as a plenary session at ASCO and published in the New England Journal of Medicine. Furthermore, RVD has been established as a backbone to which next generation agents are being added, including elotuzumab, daratumumab and isatuximab.
He has published extensively, having authored or co-authored over 460 original articles and 340 reviews, chapters, and editorials in peer-reviewed journals. In addition to holding positions on the Editorial Boards of leading journals, he is prior Chairman of the Multiple Myeloma Research Consortium (MMRC), Clinical Trials Core, a position held for 5 years as part of a rotating tenure, and for which he continues as a member of the Steering and Project Review Committee. He was also a member of ASCO Hematologic Malignancies Subcommittee for the required one-year term, and then for one year on the ASCO Internet Cancer Information Committee during 2017. He was appointed Chair of the Alliance Myeloma Committee in 2011 and completed his 10-year tenure in this role in 2021, and then served for one more year on the committee in an emeritus role.
Honors include the George Canellos Award for Excellence in Clinical Research and Patient Care, and The Tisch Outstanding Achievement Award for Clinical Research, as well an honorary Fellowship of the Royal College of Physicians (UK), given in recognition for international contributions in multiple myeloma and stem cell transplantation. He was a co-recipient of the prestigious Warren Alpert Foundation Prize in recognition of the successful therapeutic targeting of the ubiquitin-proteasome pathway in 2012. He was also a co-recipient of the Accelerator Award for contributions to clinical research and patient enrollment in MMRC studies, as well as for the Research Center of the Year Award in 2009, followed by a second award for Center of the Year in 2017. He was ranked by Thomson Reuters Science Watch amongst the top 19 investigators at DFCI for the most highly cited research in 2016 and again in 2022. He was the co-recipient of the ASH Ernest Beutler Prize for clinical science and translational research in the development of proteasome inhibition as an effective treatment strategy for multiple myeloma in 2015; the COMY Award for MM research (Paris, France) in 2016, and the prestigious IMF Robert A. Kyle Lifetime Achievement Award in 2017, together with the Clare and Richard Morse Research Award (DFCI) in 2019, as well as the Giants of Cancer Care Award (USA) in 2021, followed by the inaugural James Griffin team award for outstanding translational clinical research award (DFCI) in 2023.
Dr. María-Victoria Mateos
María-Victoria Mateos is Consultant Physician in the Haematology Department and Associate Professor of Medicine at the University of Salamanca, Spain. She is the director of the Myeloma Program and coordinates 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 elderly and smouldering MM patients that have profoundly influenced current options for treating these patient populations.
She has published over 200 original papers in international journals. Her areas of interest include multiple myeloma, the biology of plasma cells and the development of new drugs.
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