In longer-term 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. The findings, which report results from 24 months of maintenance therapy, were presented at the 2021 American Society of Hematology Annual Meeting.
According to the study authors, the results support use of daratumumab plus RVd induction and consolidation with daratumumab maintenance in transplant-eligible patients with newly diagnosed disease.
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.
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).
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.