Daratumumab (DARA) is a human IgGκ anti-CD38 monoclonal antibody with a direct on-tumor and immunomodulatory mechanism of action. In combination with standard of care (SOC) regimens, DARA has consistently demonstrated a doubling of complete response (CR) rates, tripling of minimal residual disease (MRD)-negative rates, and reduction in the risk of progression or death by ≥50% vs SOC alone in relapsed/refractory MM and NDMM pts. In the prespecified interim analysis of ALCYONE, a phase 3 study of D-VMP versus VMP in transplant ineligible NDMM (Mateos MV, N Engl J Med 2018. 378:518-528), significant progression-free survival (PFS) benefit (median not reached [NR] vs 18.1 mo; hazard ratio [HR], 0.50; P <0.001) and a higher rate of MRD negativity (10–5 threshold: 22% vs 6%; P <0.001) were observed without increased overall toxicity for D-VMP versus VMP after a median follow-up of 16.5 months. This report provides updated efficacy and safety findings from ALCYONE after 1 year of additional follow-up.
With 1 year of additional follow-up, the combination of DARA and VMP in transplant ineligible NDMM pts continues to demonstrate a significant PFS benefit, including in pts ≥75 years of age, and allows for maintenance of PFS benefit during the subsequent line of therapy. Improvements in duration and depth of response continue to be observed with D-VMP with longer follow-up. No new safety signals emerged following the addition of DARA to VMP, and grade 3/4 infections continue to be manageable with no notable increase in rates. These results continue to support the use of D-VMP in the first line of treatment in transplant ineligible NDMM.
Meletios A Dimopoulos, MD, Maria-Victoria Mateos, MD, PhD, Michele Cavo, MD, Kenshi Suzuki, MD, PhD, Andrzej Jakubowiak, MD, PhD, Stefan Knop, Chantal Doyen, MD, Paulo Lucio, Zsolt Nagy, MD, PhD, Polina Kaplan, Ludek Pour, MD, Mark Cook, MBChB, PhD, Sebastian Grosicki, MD, PhD, Andre H Crepaldi, MD, Anna Marina Liberati, MD, Philip Campbell, MBBS, FRACP, FRCPA, Tatiana Shelekhova, Sung-Soo Yoon, MD, PhD, Genadi Iosava, MD, Tomoaki Fujisaki, MD, PhD, Mamta Garg, Christopher Chiu, PhD, Jianping Wang, Anupa Kudva, MD, Rachel Kobos, MD, Susan Wroblewski, PhD, Ming Qi, MD, PhD, Jesus F San-Miguel, MD, PhD and Joan Bladé, MD, PhD
156 One-Year Update of a Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Patients (Pts) with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): Alcyone
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.