The meeting started with discussions on Precursor Conditions, chaired by Mario Boccadoro and Sigurdur Y. Kristinson. Brian A. Walker presented current data in the genomic evolution of these conditions presenting the evolution form the germinal B cell to MGUS, SMM and MM. This evolution requires changes in the immune microenvironment and their role during the evolution from MGUS to SMM and MM was discussed by Madhav Dhodapkar. Dr Niels Weinhold discussed evidence on the timing of molecular changes that occur during evolution of precursor conditions, followed by S. Vincent Rajkumar who presented current evidence on the clinical and laboratory risk factors for MGUS/SMM progression. María-Victoria Mateos presented current and future directions of management of smoldering myeloma and Irene Ghobrial discussed whether there is evidence that could be used to recommend a systematic screen for precursor conditions.
This session was followed by presentations on the approach to multiple myeloma diagnosis and clinical risk stratification. Chaired by P. Joy Ho and Shaji K Kumar, who also presented the current diagnostic criteria and work-up. Dr Herve Avet-Loiseau discussed the definitions of standard and high-risk mm in 2022 and Dr Elena Zamagni discussed the advancing role of imaging in the diagnosis and response assessment. Dr Bruno Paiva presented data in the advancing role of assessment of circulating tumor cells and tumor DNA for prognosis and for response assessment while Dr Dave Murray showed data regarding the potential of using mass-spectrometry to monitor the treatment response and minimal residual disease. Finally, Dr Alessandra Larocca emphasized the importance of assessment of patient frailty and functional status, advocated for a complete evaluation of a patient with myeloma, especially in older patients.
One of the most interesting sessions of the first day was the joint discussion of Drs Nikhil Munshi, Brian Durie and Jesus San Miguel on present unmet needs in myeloma. They were joined by Nicole Gormley from FDA and Jorge Camarero from EMA, who shared perspectives on the regulatory considerations for the approvals of new therapies and the relevant end points of clinical trials from the view point of these organizations.
The second day of the workshop started with the presentation of current treatment approaches in newly diagnosed multiple myeloma, chaired by Drs David S. Siegel and María-Victoria Mateos. Dr Philippe Moreau presented the current data on the induction therapy for transplant-eligible newly diagnosed Myeloma patients. Dr Michele Cavo discussed the role of ASCT in newly diagnosed myeloma patients and Dr Pieter Sonneveld the current approaches to consolidation strategies for MM after ASCT while Dr Harmut Goldschmidt the existing and future maintenance strategies for MM after ASCT. Finally, Dr Thierry Facon provided updates on the treatment approaches for non-transplant eligible newly diagnosed myeloma patients.
In the oral abstract session, chaired by Drs Edward Stadtmauer and Lugui Qiu, five abstracts were presented. Dr Philippe Moreau presented updates on the overall survival and progression-free survival by treatment duration from the MAIA study which compared the triplet of Daratumumab with Lenalidomide/Dexamethasone vs Lenalidomide/Dexamethasone in transplant-ineligible newly diagnosed Multiple Myeloma patients. Dr Rakesh Popat presented data on the use of carfilzomib maintenance following ASCT or carfilzomib-cyclophosphamide-dexamethasone (KCd) consolidation for newly diagnosed multiple myeloma (MM). Dr Roberto Mina presented and analysis from the FORTE trial [Carfilzomib-Based Induction/Consolidation With or Without Autologous Transplant and Lenalidomide (R) or Carfilzomib-Lenalidomide (KR) Maintenance] in patients with high-risk myeloma. Dr Enrique Ocio updated on the Safety and Efficacy of Isatuximab given as a short-duration fixed-volume infusion with Bortezomib, Lenalidomide, and Dexamethasone patients with NDMM who were either ineligible or with no intent for Immediate for ASCT. Finally, Dr Andrzej Jakubowiak presented data regarding the efficacy of Daratumumab-based regimens (DRd and D-VMP) transplant-ineligible, high-risk, newly diagnosed multiple myeloma (NDMM)
Dr Meral Beksac and Dr Gösta Gahrton chaired the session on the Management of patients with relapsed/refractory myeloma. Dr Bob Orlowski discussed the Management of triple refractory patients; Dr Saad Z. Usmani provided a comprehensive update on the role of immunotherapies for relapsed myeloma and Dr Marc-Steffen S Raab pointed on the potentials of personalized treatment of relapsed MM through the use of genomics.
This session was followed by an oral abstract session chaired by Natalie S. Callander and Merav K. Leiba. First, Dr Martin F. Kaiser presented the results regarding the depth of response and MRD negativity in patients with newly diagnosed molecularly stratified ultra-high-risk myeloma and plasma cell leukemia who were treated with multi-drug combination of Dara-CVRd and followed by bortezomib-high dose melphalan and ASCT (from the UK OPTIMUM/MUKnine trial). Dr Sagal Lonial presented data on the activity of the combination of Iberdomide with dexamethasone daratumumab, bortezomib, or carfilzomib (CFZ) in patients with relapsed/refractory multiple myeloma. A. Cathelijne Fokkema presented data from single cell RNAseq analysis of circulating tumor cells in newly diagnosed patients and their association with increased proliferation markers on bone marrow paired samples. Dr Ruth De Tute presented data on the impact of lenalidomide on maintenance MRD following ASCT, the prognostic significance of MRD of the molecular risk in myeloma patients treated in the Myeloma XI trial. Dr Aurore Perrot presented the data regarding the treatments of patients with multiple myeloma from a large registry of the nationwide French National Claim database, from 2014 to 2019.
On Friday morning, Dr Kenneth C. Anderson and Pieter Sonneveld chaired the IMS-EHA joint-symposium on Immune Therapies, Dr Gilles Salles presented data on new immune therapies and combinations in lymphoma, and Dr John Gribben discussed new immune approaches in hematologic malignancies, and especially in lymphomas.
In the oral abstract session that followed and was chaired by Michael O’Dwyer and Dr Tomas Jelinek, there were presentations from studies with immune therapies, including CAR-T cell-based and bispecific-based therapies. Dr Adam D. Cohen presented the initial results, in 20 patients, on the efficacy and safety of ciltacabtagene autoleucel (a BCMA-directed CAR-T cell therapy), from CARTITUDE-2 study, in patients with progressive multiple myeloma after 1–3 prior lines of therapy, while Prof. Sundar Jagannath presented the updated results from CARTITUDE-1 with Ciltacabtagene autoleucel in relapsed/refractory multiple myeloma patients that had received ≥3 prior regimens. Dr Niels W.C.J. van de Donk presented updated results of a phase 1, first-in-human study, of Talquetamab, a bispecific antibody targeting G protein-coupled receptor family C group 5 member D (GPRC5D) bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Dr Bhagirathbhai Dholaria presented results from the MagnetisMM-1 study which evaluated elranatamab (PF-06863135), a B-cell maturation antigen (BCMA) targeted CD3-engaging bispecific antibody in patients with relapsed/refractory myeloma. Finally, Dr Larry D. Anderson, Jr presented updated results from the KarMMa study of Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, in 128 patients with relapsed and refractory multiple myeloma that received the treatment.
Dr Jorge Castillo and Professor Giampaolo Merlini directed the discussions of other plasma cell malignancies. Dr Giovanni Palladini presented the current strategies for patients with AL amyloidosis, Dr Steve Treon novel approaches in management of WM, Dr Joan Blade the concepts of Monoclonal gammopathy of clinical significance and Dr Nelson Leung an update on monoclonal gammopathy of renal significance
In the oral abstract session chaired by Dr Angelo Maiolino and Dr Jens Hillengass. Dr Shaji Kumar presented an analysis from the ANDROMEDA Study that compared Daratumumab with VCD vs VCD in newly diagnosed patients with AL amyloidosis that was focused on the impact of cytogenetic abnormalities on treatment outcomes. Dr Rosalinda Termini presented data on the use of minimally invasive profiling with flow cytometry in peripheral blood of tumor and immune cells to risk stratify patients with smoldering multiple myeloma (iMMunocell study). Dr Eli Mucthar presented two abstracts, one with an analysis of new Graded Renal Response Criteria and Revised Renal Progression Criteria for Light chain Amyloidosis and a second on graded Cardiac Response Criteria assessing the Impact of Depth of Cardiac Response on Survival. Dr Alissa Visram presented an analysis that assessed the prognostic utility of the Mayo 2018 and IMWG 2020 smoldering multiple myeloma risk stratification scores but when applied post diagnosis of the SMM.
The next abstract session was chaired by Dr Elisabet Manasanch and Dr Jae Hoon Lee. Dr Fredrik Schjesvold presented data from the OCEAN (OP-103) study, a phase 3, randomized, study that compared Melflufen and Dexamethasone to Pomalidomide and Dexamethasone in relapsed refractory multiple myeloma patients. Dr Luciano J Costa presented an MRD response-adapted treatment duration with Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (Dara-KRd) and cessation of therapy in newly diagnosed multiple myeloma patients who received induction with Dara-KRd followed by Autologous Transplantation. Dr Oliver Van Oekelen presented data regarding the clinical outcomes of myeloma patients after BCMA-targeted CAR T cell therapy. Dr Romanos Sklavenitis-Pistofidis presented data that Single-cell RNA-sequencing can identify immune biomarkers of response to immunotherapy in patients with high-risk Smoldering myeloma treated with Elotuzumab, Lenalidomide, and Dexamethasone. Prashant Kapoor presented and analysis on the impact of chromosome 1 abnormalities on newly diagnosed multiple myeloma who were treated in the ENDURANCE ECOG-ACRIN E1A11 trial (with either KRd or VRd).
One of the most exciting sessions was the “Great Debates in Myeloma” session. Dr Romak Hajek, Dr Harmut Goldschmidt, Dr Heinz Ludwig and Dr Hermann Einsele moderated these debates between myeloma experts that covered hot topics in the management of the disease. In the question whether every transplant eligible NDMM patient should receive a transplant, Dr Sergio Giralt supported the ‘yes’ position and was challenged by Dr Morie Gertz. Prof Sundar Jagannath debated with Dr Ola Landgren whether we are ready for an MRD-guided therapy in myeloma. In the question regarding stratification based on genomics and their use in clinical practice Dr Gareth Morgan supported the ‘pro’ position against Dr Faith Davies. Dr Hermann Einsele supported the premise that the best immune approach to replace ASCT is Bispecific antibodies while Dr Parameswaran Hari presented arguments to support the use of CAR T cells. Dr Luciano J Costa provided arguments supporting treatment-free intervals and was challenged by Dr Philip l. McCarthy. Finally, Dr Donna Reece maintained that there is still a role for alkylator in MM while Dr Jeffrey L. Wolf argued the opposite.
In the session dedicated to immunotherapy, chaired by Dr Ivan Borrello and Dr Qing Yi, there were extensive presentations of many topics of special interest. Dr Yi Lin presented the mechanisms of resistance to CAR-T cells and bispecifics, and Dr Michael Hudecek potential strategies to improve the efficacy of CAR-T cells and bi-specifics. Dr Roman Hajek discussed the concept and development of Allo-CAR-T cells and Dr Adam D. Cohen presented on CAR- NK cells. Dr David Avigan concluded with data on vaccination therapies for myeloma.
The last session of the meeting was dedicated to a presentation on Clinical Trials in Progress, chaired by Dr Raymond Comenzo and Dr William Bensinger. Dr Jonathan L Kaufman presented ongoing and future studies from North America, Dr Xavier Leleu from Europe, Dr Vania Hungria from South America, Dr Jeffrey SY Huang from Asia and Dr Hang Quach from Australia.