Daratumumab Plus Bortezomib, Melphalan y Prednisone Versus Bortezomib, Melphalan y Prednisone en pacientes con mieloma múltiple recién diagnosticado no elegible para trasplante: supervivencia general en alcyone
Introduction: Daratumumab (DARA) is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. The addition of DARA to standard-of-care regimens in phase 3 studies reduced the risk of disease progression or death by ≥44%, nearly doubled the rate of complete response or better, and induced a ≥3-fold increase in minimal residual disease (MRD)–negativity rates versus standard of care alone in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) and relapsed/refractory multiple myeloma. In the primary analysis of the phase 3 ALCYONE study (median follow-up: 16.5 months), a significant progression-free survival (PFS) benefit (median not reached vs 18.1 months; hazard ratio [HR], 0.50; P <0.001) was observed with the addition of DARA to bortezomib/melphalan/prednisone (D-VMP) in patients with transplant-ineligible NDMM, without an increase in overall toxicity (Mateos MV, et al. N Engl J Med. 2018;378:518-528). D-VMP continued to demonstrate a significant PFS benefit versus VMP alone after 1 year of additional follow-up, including in patients ≥75 years of age (Dimopoulos MA, et al. Blood. 2018;132[Suppl 1]:156). After a median follow-up of 27.8 months, D-VMP reduced the risk of disease progression or death by 57% versus VMP alone, with a 24-month PFS rate of 63% in the D-VMP group and 36% in the VMP group. This PFS benefit was observed regardless of patient age and was maintained during the subsequent line of therapy in patients with transplant-ineligible NDMM. Here, we present >36 months of follow-up from ALCYONE, including analysis of overall survival (OS) from a prespecified interim analysis.
Conclusions: For the first time, we demonstrate that the addition of DARA to VMP prolongs OS in patients with transplant-ineligible NDMM, with a 40% reduction in the risk of death versus VMP alone after a median follow-up of 40 months. D-VMP continued to demonstrate a significant PFS benefit, which was also maintained during the subsequent line of therapy. These findings, together with the phase 3 MAIA study (DARA plus lenalidomide/dexamethasone vs lenalidomide/dexamethasone), continue to support the addition of DARA to frontline treatment regimens in patients with transplant-ineligible NDMM.
ABOUT MARIA V. MATEOS, MD, PhD
Dr. María-Victoria Mateos is an Associate Professor of Hematology and Consultant Physician in the Haematology Department at the University of Salamanca and Director of the Myeloma Unit, where she is responsible for coordinating the Clinical Trials Unit in Salamanca University Hospital’s Hematology Department. She currently serves on the European Hematology Association (EHA) as the Chair of the Scientific Program Committee for the 2019 Congress