IMF RESEARCH
The Black Swan Team discusses the progress of the ongoing “Cure” Trials. [From Left:] María-Victoria Mateos, MD, Phd (University of Salamanca — Spain); IMF Chairman of the Board Brian G.M. Durie, MD; Bruno Paiva, PhD (University of Navarro — Pamplona, Spain); Shaji Kumar, MD (Mayo Clinic — Rochester, MN); and S. Vincent Rajkumar, MD (Mayo Clinic — Rochester, MN).
THE BLACK SWAN RESEARCH INITIATIVE’S ONGOING PROJECTS The International Myeloma Foundation’s signature research project, the Black Swan Research Initiative® (BSRI®), fueled by a team of multinational myeloma researchers, continues to make strides. Below is a follow-up on BSRI projects that have been ongoing since 2016. •
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Recent minimal residual disease (MRD) research focuses on Next Generation Flow testing in the blood (versus in the bone marrow) for disease monitoring. Early published results demonstrate the value of serial blood monitoring. New data emerging in the future will possibly validate the approach of combining NGF testing with mass spectrometry testing. This combined testing approach may reduce the need for frequent bone marrow testing. The ASCENT trial (Aggressive Smoldering Curative Approach Evaluating Novel Therapies) continues to evaluate the efficacy and safety of the combination of Darzalex® (daratumumab), Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone in high-risk smoldering multiple myeloma (HRSMM). Its goal: to learn whether starting treatment early substantially improves outcomes, leads to a higher level of undetected MRD, to sustained remissions, and to a potential cure. The trial continues to accrue participants, and its early results are very promising. The CESAR trial is ongoing in Spain with Professor María-Victoria Mateos as the Principal Investigator. CESAR (Curativo Estrategia Smouldering Alto Riesgo, or Curative Strategy for High-Risk Smoldering) uses the combination of Kyprolis, Revlimid, and dexamethasone (KRd) with autologous stem cell transplant in the same setting as ASCENT. With a three-year follow-up reported at the American Society of Hematology annual conference in December 2019, 62% of patients have achieved deep responses and are MRD-negative at 10 -6 level, or zero out of one million bone marrow cells.
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Finally, for patients not achieving MRD-negative status, many BSRI projects focus on characterizing the disease as residual and/or relapsing. Dr. Andrew Spencer in Australia leads a BSRI-supported team to evaluate DNA in the blood—so-called cell free or cfDNA. The team has observed a range of mutations that can serve as a basis for possible new treatment strategies for patients with residual disease.
ISTOPMM FORGES AHEAD IN 2020 In November 2016, the Iceland-based iStopMM (Iceland Screens, Treats, Or Prevents Multiple Myeloma) project was launched in Reykjavík. The project’s ambitious screening process to identify new patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM) has been successful beyond all expectations, with more than 80,000 individuals screened and tested to date. The hard work continued as the team worked to understand as much as possible. Topline Questions from the Study: What clues might point to possible causes for MGUS/SMM/MM? A major reason for conducting this project in Iceland is that full DNA sequencing is available through deCODE Genetics for all participants. Because of this, genetic predisposing factors can be accurately assessed. In addition, participants’ full medical histories are available, including family history, occupations, and details of all medical interventions (such as surgeries) and medications used. Diet has already been closely studied. The possible triggering role of infections will now be explored in a new collaboration with investigators in another Black Swan project in France. These French investigators are studying if myeloma is being driven by infections such as hepatitis C or the Epstein-Barr virus. Initial results will be available soon.
