Daratumumab is a novel monoclonal antibody that specifically targets tumors expressing the glycoprotein CD38, inducing potent cytotoxic effects.1 It was recently approved for the treatment of patients with relapsed and refractory multiple myeloma (MM) based on the safety and efficacy demonstrated in 2 open-label clinical trials, GEN501 and Sirius.2 GEN501 is a 2-part (part 1, dose escalation; part 2, dose expansion) study in patients who had relapsed after or were refractory to ?2 prior therapies; Sirius is a 2-part phase 2 study of patients with MM with ?3 prior therapies, including a protease inhibitor (PI) or immunomodulatory drug (IMiD), or were refractory to both a PI and an IMiD.3,4 Usmani and colleagues reported on the results of a combined efficacy analysis of patients treated with daratumumab 16 mg/kg in Sirius and part 2 of GEN501.5 The combined analysis included 148 patients, of which 42 were from GEN501 and 106 were from Sirius studies. In the combined analysis, the objective response rate (ORR) was 31%, and the rate of very good partial response or better was 13%, with 2 patients achieving complete responses (CRs) and 3 achieving stringent CRs. Moreover, responses were reported to deepen with continued daratumumab therapy. At a median follow-up of 14.8 months, the median duration of response was 7.6 months, and 50% of responders remained progression-free at 1 year. After a median follow-up of 14.8 months, the estimated median overall survival (OS) was 19.9 months; the estimated 1-year OS rate was 69%. Notably, daratumumab therapy also conferred OS benefit even in patients who achieved stable disease and minimal response, with a median OS of 17.5 months. No new safety signals were identified in the combined analysis, with the safety profile consistent with those previously identified in the individual GEN501 and Sirius studies. Overall, common all-grade adverse events included fatigue (41%), nausea (28%), anemia (28%), back pain (24%), cough (22%), neutropenia (20%), thrombocytopenia (20%), and upper respiratory tract infections (20%). Grade 3/4 adverse events were mostly hematologic, including anemia (18%), neutropenia (10%), and thrombocytopenia (14%); 3 patients each experienced fatigue and back pain. Infusion-related reactions were experienced by 48% of patients, the majority of which occurred in the first cycle. These results support the previous results of remarkable clinical activity of daratumumab in heavily pretreated patients with MM.
