Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma

作者：Antonio Palumbo, Asher Chanan‐Khan, Katja Weisel, Ajay K. Nooka, Tamás Masszi, Meral Beksaç, Ivan Špıčka, Vânia Hungria, Markus Munder, María‐Victoria Mateos, Tomer M. Mark, Ming Qi, Jordan M. Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Andrew Spencer, Pieter Sonneveld · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1606038 · 被引用次数：1530 · 研究领域：Multiple Myeloma Research and Treatments、Viral-associated cancers and disorders、Immunotherapy and Immune Responses

BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete ...