The GMMG-HD6 study is an ongoing phase 3, randomized, open-label, multicenter trial examining the effect of bortezomib, lenalidomide, and dexamethasone (VRD) with or without the addition of elotuzumab (Elo) as induction therapy for newly diagnosed transplant-eligible patients with multiple myeloma. The trial will primarily evaluate whether the addition of elotuzumab to a high-dose chemotherapy regimen of VRD is able to improve progression-free survival compared with the same regimen without elotuzumab, with secondary end points of overall survival and complete response rates following the induction therapy comparing the VRD arm with the VRD + Elo arm. The safety profile will also be evaluated.
The study design includes 4 groups of patients randomized into 4 study arms: A1, A2, B1, and B2. The patients in the A1 and A2 arms (n = 280) receive four 21-day induction cycles of VRD, and patients in arms B1 and B2 (n = 279) are administered the same VRD regimen with the addition of elotuzumab. The baseline characteristics of the patients include a median age of 59 years (range, 27-70 years), with International Staging System stages, high-risk cytogenetics including del(7p13), t(4;14), or >3 copies of 1q21, and proportion of patients with renal impairment being equally distributed among the arms. At least 4 induction cycles were completed by 94.3% of the VRD group and 92.5% of the VRD + Elo group. Discontinuation until 30 days after induction therapy occurred for 21 patients in the VRD group and 25 patients in the VRD + Elo group due to toxicity, progressive disease, death, or withdrawal of consent.
After the fourth cycle of induction therapy with VRD or VRD + Elo, overall response rate (≥partial response) was 85.6% in the VRD group and 82.4% in the VRD + Elo group. Very good partial response or better was achieved by 54% of patients given VRD and 58.3% of patients given VRD + Elo. Complete response was achieved by 3.6% of patients given VRD and 2.9% of patients given VRD + Elo.
At least 1 adverse event (any grade) during the induction period was observed in 66.5% of the safety population of the VRD group and in 65.4% of the safety population of the VRD + Elo group (VRD: n = 183/275, 66.5% vs VRD + Elo: n = 183/280, 65.4%; P = .79). Most common system organ classes were nervous system disorders (VRD: 24.0% vs VRD + Elo: 23.6%; P = .92), infections and infestations (VRD: 22.9% vs VRD + Elo: 20.0%; P = .41), and blood and lymphatic system disorders (VRD: 8.4% vs VRD + Elo: 14.6%; P = .02). There were 4 deaths in the VRD group and 9 deaths in the VRD + Elo group related to the induction therapy.
The addition of elotuzumab to VRD for 4 induction cycles for newly diagnosed patients with multiple myeloma did not increase the rate of very good partial response or better after 4 induction cycles. Evaluation of patients at later time points to assess overall response rates will occur in further trial analysis.
Reference
- Abstract and Presentation S203. EHA 2020. June 12, 2020. Bortezomib, lenalidomide and dexamethasone with or without elotuzumab as induction therapy for newly diagnosed, transplant-eligible multiple myeloma.