Belantamab mafodotin, bortezomib, dexamethasone triplet scores big in RRMM

Triplet therapy with belantamab mafodotin, bortezomib, and dexamethasone (BVd) significantly improves outcomes in relapsed or refractory multiple myeloma (RRMM), outperforming the daratumumab, bortezomib, and dexamethasone (DVd) combination therapy, according to the second interim analysis of the phase III DREAMM-7 trial.

DREAMM-7 included 494 adult patients (median age 64.5 years, 55 percent male, and 83 percent White) with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and progression on or after at least one previous line of therapy.

The patients were randomly assigned to receive BVd (n=243) or DVd (n=251). The BVd group received belantamab mafodotin 2.5 mg/kg intravenously every 3 weeks; bortezomib 1.3 mg/m² subcutaneously twice weekly in 21-day cycles, for up to eight cycles; and dexamethasone 20 mg orally or intravenously on the day of and after bortezomib treatment for up to eight cycles. The DVd group received daratumumab 16 mg/kg intravenously in 21-day cycles—once weekly in cycles 1–3, every 3 weeks in cycles 4–8, and every 4 weeks in cycle 9 and beyond; and bortezomib and dexamethasone, with their doses and schedules being the same as those in the BVd group.

The primary endpoint was progression-free survival (PFS), while key secondary endpoints included overall survival (OS), minimal residual disease negativity in patients with a complete response or better, duration of response to treatment, and safety.

Over a median follow-up of 39.4 months, BVd conferred early, sustained, and significant OS benefit compared with DVd. Median OS was not reached (NR) with both BVd (95 percent confidence interval [CI], NR–NR) with BVd and DVd (95 percent CI, 41.0–NR) (hazard ratio [HR], 0.58, 95 percent CI, 0.43–0.79; p=0.0002).

In the subset of patients with a complete response or better, BVd-treated patients were more likely than those who received DVd to have minimal residual disease-negativity (25 percent vs 10 percent) and longer median duration of response (40.8 vs 17.8 months).

Results of the second PFS analysis favoured BVd over DVd, with PFS maintained following subsequent antimyeloma therapy. The median PFS 2 was NR (95 percent CI, 45.6–NR) with BVd vs 33.4 months (95 percent CI, 26.7–44.9) with DVd (HR, 0.59, 95 percent CI, 0.45–0.77).

In terms of safety, thrombocytopenia was the most common grade 3 or 4 adverse event (56 percent with BVd vs 35 percent with DVd). Serious adverse events, including pneumonia, pyrexia, and COVID-19, occurred in 53 percent and 38 percent, respectively. Treatment-related serious adverse events that led to death occurred in 3 percent of patients in the BVd group and in 1 percent in the DVd group.