Peter Voorhees, MD – Director of Outreach for Hematologic Malignancies at Atrium Health’s Levine Cancer Institute speaks about ASH 2020 Abstract – 549 Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy.
Introducing:
DARA, a human IgG Ange monoclonal antibody targeting CD38, is approved for relapsed/refractory multiple myeloma and NDMM as monotherapy and in conjunction with normal treatment regimens. In the primary review of the phase 2 GRIFFIN (NCT02874742) study, DARA plus RVd (D-RVd) significantly improved rigid complete response (sCR) rates in patients with transplant-eligible NDMM by the end of post-transplant consolidation therapy versus RVdd (RVd) (Voorhees P, Blood 2020). After 12 months of lenalidomide (R) or DARA plus R maintenance treatment, we present revised efficacy and safety findings here (D-R)Â (D-R).
Methods:Â
Methods: Patients received 4 cycles of induction, HDT, ASCT, 2 cycles of consolidation, and 24 months of maintenance with R ± DARA. Patients got R 25 mg PO on Days 1-14; V 1.3 mg/m2 SC on Days 1, 4, 8, and 11; and d 40 mg QW every 21 days during induction and consolidation. On days 1, 8, and 15 of Cycles 1-4 and day 1 of Cycles 5-6, DARA 16 mg/kg IV was given. Patients obtained R 10 mg (15 mg in Cycles 10+ if tolerated) during maintenance (Cycles 7-32) on Days 1-21 every 28 days ± DARA 16 mg/kg IV Q8WW on Days 1-21 (or Q4W per patient decision after Amendment 2). The primary endpoint was the sCR rate calculated by a validated computer algorithm, at the end of the post-ASCT consolidation per IMWG criteria. Progression-free survival (PFS) and rate of minimal residual disease (MRD) negativity (10-5 threshold per IMWG criteria) evaluated by next-generation sequencing were the main secondary endpoints (clonoSEQ; Adaptive Biotechnologies). At a 1-side alpha of 0.10., the primary hypothesis was tested. A 2-sided P value (alpha 0.05) was used to test all the secondary tests and was not adjusted for multiplicity.
Outcomes:
There were 207 patients randomized in total (D-RVd, n=104; RVd, n=103). Baseline demographics and disease features between guns were well balanced. The sCR rate favored D-RVd versus RVd (42.4 percent [42/99] vs 32.0 percent [31/97]; 1-sided P=0.0680) at the end of the post-transplant consolidation (median follow-up, 13.5 months) in the response-evaluable population. Responses tended to deepen and stayed higher for the D-RVd group than the RVd group with additional D-R or R maintenance therapy. The sCR rate still favored D-RVd versus RVd (63.6 percent [63/99] vs 47.4 percent [46/97], 2-sided P=0.0253; Figure) at the 12-months-of-maintenance therapy data cut (median follow-up, 26.7 months). In the ITT population, MRD-negativity (10-5) concentrations favored D-RVd versus RVd (62.5% [65/104] vs 27.2% [28/103], P<0.0001; Figure), as well as in patients who at that time obtained full response (CR) or better (76.5% [62/81] vs 42.4% [25/59], P<0.0001). Similarly, in the ITT population (26.9 percent [28/104] vs 12.6 percent [13/103], P=0.0140; Figure), MRD-negativity (10-6) rates favored D-RVd versus RVd as well as in patients who obtained CR or better at that time (34.6 percent [28/81] vs 18.6 percent [11/59], P=0.0555). Estimated 24-month PFS rates were 94.5 percent and 90.8 percent for the D-RVd and RVd classes respectively. There were 14 deaths in total (n=7 per group), and 9 were due to progressive illness (D-RVd, n=5; RVd, n=4). No new safety issues were found with longer follow-up. In the D-RVd group, 84.8 percent (84/99) and 79.4 percent (81/102) of patients in the RVd group had Grade 3/4 treatment-emergent adverse events (TEAEs). In the RVd party, one grade 5 TEAE occurred, unrelated to study therapy (unknown cause). 43.4 percent (43/99) of patients had infusion-related reactions, the majority of which were grade 1 or 2 and occurred in the first cycle.
Findings:
After 26.7 months of median follow-up, deep and enhanced responses, including higher sCR and MRD negativity rates compared with lenalidomide alone, continued to be demonstrated with the addition of DARA to RVd induction and consolidation, accompanied by D-R maintenance in patients with transplant-eligible NDMM. In comparison to post-consolidation rates, maintenance therapy improved sCR and MRD negativity rates. With longer follow-up, no new safety issues were found.