Over half of patients with newly diagnosed multiple myeloma (NDMM) are ineligible for autologous stem cell transplantation. For these patients, a combination therapy consisting of the proteasome inhibitor bortezomib with melphalan and prednisone is one of the preferred treatments. Adding daratumumab to standard regimens for transplant-ineligible NDMM and relapsed/refractory multiple myeloma has had promising results. Now, data from the phase 3 ALCYONE trial show that adding daratumumab to bortezomib/melphalan/prednisone (VMP) increases overall survival in patients with transplant-ineligible NDMM. In this interview with i3 Health, Maria Victoria Mateos, MD, PhD, the principal investigator of ALCYONE, discusses this latest data, which she is presenting today at the American Society of Hematology (ASH) Annual Meeting and Exposition, and she shares her thoughts on additional progress that is being made in the treatment of transplant-ineligible NDMM.
Can you comment on the significance of your study's results regarding the addition of daratumumab to VMP for transplant-ineligible NDMM?
Maria Victoria Mateos, MD, PhD: The update of this phase 3 clinical trial shows that with a median follow-up of 40 months, the addition of daratumumab to a standard-of-care regimen like VMP continues demonstrating a significant benefit in terms of progression-free survival, but the most important news is the benefit in overall survival, with a hazard ratio of 0.60, meaning that the treatment with daratumumab/VMP reduced the probability of death by 40% compared with VMP alone.
What additional treatment advances are on the horizon for transplant-ineligible NDMM?
Dr. Mateos: The main advance is the addition of the monoclonal antibodies targeting CD38 to the different standard-of-care regimens for this population. Together with daratumumab/VMP, daratumumab added to lenalidomide/dexamethasone is another regimen already approved by both the FDA and the European Medicines Agency (EMA), so it is also a new standard of care. The next one will be daratumumab added to bortezomib/lenalidomide/dexamethasone, also in this population. With all these combinations, almost all patients respond. The overall response rates are over 90%, and most importantly, 50% of patients achieve complete response. Overall, one out of three patients can achieve minimal residual disease (MRD) negativity sustained over time, which is an excellent surrogate marker for both progression-free and overall survival.
What are the greatest challenges of treating patients with transplant-ineligible NDMM?
Dr. Mateos: There are two. The first challenge is to achieve a correct evaluation of the transplant-ineligible patient with newly diagnosed myeloma, putting together the chronological age with the biological one, comorbidities, disabilities, and social conditions. The second is to individualize the treatment as much as possible according to the disease and patient characteristics in order to deliver the best therapy to each patient. The optimal goal of treatment in this population with transplant-ineligible NDMM would be to reach an expected overall survival comparable to the overall survival for all NDMM patients.
What advice can you offer to community hematologists and oncologists treating patients with transplant-ineligible NDMM?
Dr. Mateos: Always try to use the best combination first because the best combinations will benefit almost 100% of newly diagnosed myeloma patients. The maximum benefit is obtained from the first line of therapy, and some transplant-ineligible patients with NDMM will receive only one line of therapy.
About Dr. Mateos
Maria Victoria Mateos, MD, PhD, is an Associate Professor of Medicine and Director of the Myeloma Program at the University of Salamanca, Spain. A consultant physician in the Department of Hematology of Salamanca's University Hospital, she also coordinates the department's Clinical Trials Unit. Dr. Mateos is a member of the International Myeloma Working Group. She has served in a leadership capacity in various organizations, including ASH, the European Hematology Association, the International Myeloma Society, the Society of Hematologic Oncology, and the European School of Haematology. As a Coordinator of the Spanish Myeloma Group (GEM), she has led many important clinical trials in elderly patients with multiple myeloma and in patients with smoldering multiple myeloma. She has published over 220 papers in peer-reviewed journals.
For More Information
Mateos MV, Cavo M, Bladé J, et al (2019). Daratumumab plus bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone in patients with transplant-ineligible newly diagnosed multiple myeloma: overall survival in ALCYONE. 61st American Society of Hematology Annual Meeting & Exposition. Abstract 859.
Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of i3 Health.