According to extended follow-up from the GRIFFIN trial, the combination of daratumumab and lenalidomide, bortezomib, and dexamethasone (D-RVd) continued to provide deep and durable responses in patients with transplant-eligible, newly diagnosed multiple myeloma. These results were presented at the 2021 American Society of Hematology Annual Meeting.
The primary analysis of the phase II GRIFFIN trial, with a median follow-up of 13.5 months, showed a higher rate of stringent complete response (sCR) with D-RVd compared with RVd alone by the end of the post-AHCT consolidation. The present analysis, which included date from a median follow-up of 27.4 months, showed that the benefit persisted. After 24 months, the rate of sCR was 66.05% for D-RVd compared with 47.4% for RVd alone (p = 0.0096).
The results support use of daratumumab plus RVd induction and consolidation with daratumumab maintenance in transplant-eligible patients with previously untreated disease, the authors reported.
GRIFFIN randomized 207 patients eligible for high-dose therapy and autologous hematopoietic cell transplantation (AHCT) to receive RVd with or without daratumumab (D-RVd, n = 104; RVd, n = 103). Patients received four induction cycles of D-RVd or RVd, high-dose therapy, AHCT, two consolidation cycles, and maintenance with lenalidomide alone or with daratumumab for 24 months.
Responses deepened for D-RVd compared with RVd alone, as did rates of measurable residual disease (MRD) negativity (62.5% vs. 27.2%; p < 0.0001). These MRD benefits (to a level of (10-5) persisted after 24 months of maintenance (64.4% vs. 30.1%; p < 0.0001), and among patients who achieved complete response or better (78.0% vs. 47.5%; p = 0.0003).
Similarly, MRD negativity (10-6) also favored D-RVd compared with RVd alone in the entire study population (35.6% vs. 14.6%; p = 0.0007), as well as among those with complete response or better (42.7% vs. 22.0%; p = 0.0121).
The rate of sustained MRD negativity lasting 12 months or longer was three times greater for patients treated with D-RVd compared with RVd alone (44.2% vs. 12.6%; p < 0.0001).
The study was not powered for progression-free survival (PFS) analysis, but with a median follow-up of 38.6 months, median PFS was not reached for either treatment arm. However, the researchers said that it was trending toward favoring the daratumumab combination. The estimated 36-month PFS was 88.9% for the D-RVd arm and 81.2% for the RVd arm.
The researchers noted that there were no new safety concerns seen with this extended follow-up. Treatment-emergent adverse events leading to discontinuation were similar in both study arms. One patient in each group died due to treatment-emergent adverse events; neither death was related to the study treatment.