Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma

作者：Meletios Α. Dimopoulos, Peter M. Voorhees, Fredrik Schjesvold, Yaël C. Cohen, Vânia Hungria, Irwindeep Sandhu, Jindriska Lindsay, Ross Baker, Kenshi Suzuki, Hiroshi Kosugi, Mark‐David Levin, Meral Beksac, Keith Stockerl‐Goldstein, Albert Oriol, Gábor Mikala, Gonzalo Garate, Koen Theunissen, Ivan Špıčka, Anne K. Mylin, Sara Bringhen, Katarina Uttervall, Bartosz Puła, Eva Medvedova, Andrew J. Cowan, Philippe Moreau, María‐Victoria Mateos, Hartmut Goldschmidt, Tahamtan Ahmadi, Linlin Sha, Annelore Cortoos, Eva G. Katz, Els Rousseau, Liang Li, Robyn M. Dennis, Robin Carson, S. Vincent Rajkumar · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2409029 · 被引用次数：102 · 研究领域：Multiple Myeloma Research and Treatments、Chronic Myeloid Leukemia Treatments、Lung Cancer Research Studies

BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. RESULTS: Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active mon...