Efficacy and safety of Daratumumab, Bortezomib, Melphalan, and Prednisone (D-VMP) versus Bortezomib, Melphalan, and Prednisone (VMP) in Chinese patients with newly diagnosed Multiple Myeloma: OCTANS

Background Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38, is approved by the FDA and EMA for the treatment of newly diagnosed multiple myeloma (NDMM) in combination with standard-of-care regimens. DARA in combination with VMP (D-VMP) was approved based on results of the phase 3 ALCYONE trial. The phase 3 OCTANS study investigated the efficacy and safety of D-VMP in Asian NDMM patients (NCT03217812). Here, we present a subgroup analysis of D-VMP in Chinese patients in OCTANS. Methods Asian patients with NDMM who were ineligible for ASCT were randomized (2:1) to D-VMP or VMP. Patients received 9 (42-day) cycles of bortezomib (1.3 mg/m2 SC) twice weekly in Cycle 1 (Weeks 1, 2, 4, 5) then once weekly (QW) in Cycles 2-9 (Weeks 1, 2, 4, 5); melphalan (9 mg/m2 PO) and prednisone (60 mg/m2 PO) once daily on Days 1-4 of each cycle. DARA (16 mg/kg IV) was administered to patients in the D-VMP arm QW in Cycle 1, Q3W in Cycles 2-9, and Q4W thereafter until disease progression or unacceptable toxicity. The primary endpoint was the very good partial response or better (≥VGPR) rate. Key secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. Minimal residual disease (MRD) negativity (10–5) rate was an exploratory endpoint. Results A total of 167 Chinese patients were enrolled (D-VMP [n=114]; VMP [n=53]). Baseline characteristics were balanced between arms; median age was 69 (range, 57-81) years and 35 (21.0%) patients had high-risk cytogenetics. At the time of data analysis (clinical cutoff 2 July 2020), 31 (27.2%) patients in the D-VMP arm had discontinued treatment vs 19 (36.5%) patients in the VMP arm. At a median follow-up of 12.3 (range, 0-29.3) months for the overall study population, ≥VGPR rate was significantly improved with D-VMP vs VMP (74.6% vs 45.3%; odds ratio, 3.51; 95% CI 1.76-7.00; P=0.0003). ORR was 90.4% with D-VMP and 83.0% with VMP. Patients in the D-VMP arm achieved significantly higher MRD-negativity rates (29.8% vs 5.7%; P=0.0003). Median PFS was not reached with D-VMP vs 18.2 months with VMP (HR 0.41; 95% CI 0.21-0.78; P=0.0049); the estimated 12-month PFS rate was 83.4% vs 62.6%, respectively. The most frequent (≥10%) grade 3/4 treatment-emergent adverse events (TEAEs) for the D-VMP/VMP arms were thrombocytopenia (47.4%/44.2%), leukopenia (39.5%/48.1%), lymphopenia (38.6%/28.8%), neutropenia (37.7%/51.9%), pneumonia (32.5%/17.3%), anemia (26.3%/25.0%), hypokalemia (16.7%/3.8%), and hypertension (10.5%/11.5%). Infusion-related reactions occurred in 36 (31.6%) patients, the majority of which were mild. A total of 5 TEAE-related deaths (D-VMP, n=3; VMP, n=2) were reported. Conclusion The addition of DARA to VMP significantly improved efficacy in Chinese NDMM patients and showed a safety profile consistent with the global ALCYONE trial. No new safety concerns were identified. These data support the use of D-VMP for the treatment of Chinese NDMM patients.