Usmani and colleagues reported on the results of a combined efficacy analysis of patients treated with the anti-CD38 monoclonal antibody daratumumab in 2 trials, Sirius and part 2 of GEN501 trials, of patients with relapsed/refractory multiple myeloma (RRMM).1 Sirius is a 2-part, randomized phase 2 study in patients who had received ≥3 prior therapies, including a proteasome inhibitor or immunomodulatory drug, or were refractory to both these drug classes. 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. The study population included 148 patients; 42 patients were from the GEN501 trial and 106 were from the Sirius trial. In the combined analysis, patients achieved an objective response rate (ORR) of 31% and ≥very good partial response rate of 10%; 1% of patients achieved complete responses (CRs) and 2% achieved stringent CRs. At a median follow-up of 9.3 months, the median duration of response in the combined analysis was 7.6 months, and the 1-year progression-free survival was 46% among responders. At a median follow-up of 14.8 months, the estimated median overall survival (OS) was 19.9 months in the combined analysis; the estimated 1-year OS rate was 69%. The efficacy outcomes in the individual GEN501 trial were similar, the ORR was 36%, the estimated 1-year OS rate was 77%, and median OS had not been reached at a median follow-up of 10.2 months. In the Sirius trial, an ORR of 36% was reported, the estimated 1-year OS rate was 65%, and median OS had not been reached at median follow-up of 9.3 months. Overall, it was concluded that the results of the combined analysis supported the individual study results in demonstrating a robust clinical activity of daratumumab monotherapy in heavily pretreated patients with RRMM. Based primarily on these data, daratumumab monotherapy was approved on November 16, 2015, for the treatment of patients with MM who have received at least 3 prior treatments. Daratumumab is the first monoclonal antibody approved for the treatment of MM.
- Usmani S, et al. ASH 2015. Abstract 29.