Longer follow-up results of the phase 2 GRIFFIN trial demonstrated that the addition of daratumumab to RVd induction/consolidation in conjunction with ASCT, followed by 24 months of daratumumab-lenalidomide maintenance resulted in deep and durable responses, including stringent CR and MRD negativity rates, in patients with transplant-eligible NDMM.
Primary analysis of the phase 2 GRIFFIN trial (NCT02874742) demonstrated improvement in the rate of stringent complete response (CR) after autologous stem-cell transplantation (ASCT) consolidation with daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) versus RVd alone, in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Updated efficacy and safety results after 24 months of maintenance therapy or treatment discontinuation were presented at the 2021 ASH Annual Meeting and summarized here.
Patients with NDMM eligible for high-dose therapy (HDT) and ASCT were enrolled in the study. Eligible patients received 4 induction cycles of RVd or D-RVd, then HDT/ASCT and 2 cycles of RVd or D-RVd as consolidation, followed by maintenance with lenalidomide plus daratumumab or lenalidomide alone for 24 months. During induction and consolidation (21-day cycles), patients received a standard dose/schedule of RVd. During maintenance (cycles 7-32; 28-day cycles), patients received lenalidomide (10 mg orally on days 1-21; 15 mg after cycle 10, if tolerated) ± daratumumab (16 mg/kg intravenously) every 8 weeks (or every 4 weeks per patient decision) until disease progression or up to 24 months. Stratification was by International Staging System disease stage (I, II, or III) and creatinine clearance (30-50 mL/min or >50 mL/min). The primary end point was stringent CR rate after ASCT consolidation. Key secondary end points included progression-free survival (PFS) and minimal residual disease (MRD) negativity assessed by next-generation sequencing. Assessments were made at suspected CR or better, at the end of induction and consolidation, and after 12 and 24 months of maintenance, regardless of response.
A total of 207 patients were randomized to receive D-RVd (N = 104) or RVd alone (N = 103). Baseline characteristics were well-balanced between the 2 treatment arms. After 24 months of lenalidomide plus daratumumab or lenalidomide maintenance therapy, patients in the D-RVd group (N = 100) achieved a higher rate of stringent CR than those in the RVd group (N = 97; 66.0% vs 47.4%, respectively; P = .0096). In the intent-to-treat population, a higher rate of MRD negativity (10–5) was achieved in the D-RVd group than in the RVd group (64.4% vs 30.1%, respectively; P <.0001) that extended to patients who achieved CR or better (78.0% vs 47.5%, respectively; P = .0003). MRD negativity (10–6) rates also favored the D-RVd group versus the RVd group (35.6% vs 14.6%, respectively; P = .0007), which was higher in patients who achieved CR or better (42.7% vs 22.0%, respectively; P = .0121). The D-RVd group had significantly higher sustained MRD negativity (10–5) rates lasting ≥12 months versus the RVd group (44.2% vs 12.6%, respectively; P <.0001).
Although the study was not powered for PFS, there was a positive trend toward improved PFS in the D-RVd group compared with the RVd group at a median follow-up of 38.6 months (median PFS, not reached vs not reached; hazard ratio, 0.46). The estimated 36-month PFS rate was comparable for both groups (88.9% for D-RVd vs 81.2% for RVd).
There were no new safety signals with extended follow-up. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 86.9% (86 of 99) of patients in the D-RVd group and 79.4% (81 of 102) of patients in the RVd group. Serious TEAEs occurred in 46.5% of patients in the D-RVd group and 52.0% of patients in the RVd group. Treatment discontinuations caused by TEAEs related to study treatment occurred at the same rate in the 2 treatment arms (34.3% each). One death was reported in each group as a result of TEAEs, but neither was related to study treatment.
Longer follow-up results of the phase 2 GRIFFIN trial demonstrated that the addition of daratumumab to RVd induction/consolidation in conjunction with ASCT, followed by 24 months of lenalidomide plus daratumumab maintenance resulted in deep and durable responses, including stringent CR and MRD negativity rates with no new safety concerns, in patients with transplant-eligible NDMM.
Source: Anderson LD Jr, Kaufman JL, Laubach JP, et al. Daratumumab plus lenalidomide, bortezomib, and dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients (Pts): a subgroup analysis of Griffin. Blood. 2021;138(suppl 1):2723.