Durable clinical benefit with B-cell maturation antigen (BCMA)–directed therapy, belantamab mafodotin plus pomalidomide and dexamethasone (BPd) in relapsed/refractory multiple myeloma (RRMM): DREAMM-8 long-term responder (LTR) analysis.

Abstract

7565 Background: BCMA–directed therapies have changed the RRMM treatment landscape. In the phase 3, open-label, randomized DREAMM-8 trial (NCT04484623), BPd demonstrated significant progression-free survival (PFS) benefit compared with pomalidomide, bortezomib, and dexamethasone (PVd) in patients (pts) with RRMM who received ≥1 prior line of therapy (LOT). This post hoc analysis examined the characteristics of and outcomes in pts achieving sustained clinical benefit with BPd. Methods: DREAMM-8 is an ongoing, phase 3, open label study evaluating BPd and PVd in pts with RRMM with ≥1 prior LOT, including lenalidomide. Pts were randomized 1:1 and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever occurred first. The primary endpoint was PFS; secondary endpoints included minimal residual disease (MRD) negativity (10 -5 ), PFS2, response rates, and safety. LTRs were pts with PFS ≥30 months (data cutoff: July 7, 2025; median follow up 36 months in both arms). Results: Of the 302 pts in DREAMM-8 (BPd, n=155; PVd, n=147), 81 were LTRs. The BPd arm had more than twice the proportion of LTRs (n=59 [38%]) as the PVd arm (n=22 [15%]). Baseline characteristics between treatment arms were generally well balanced. In LTRs, median PFS potentially favored BPd (not reached [NR]; 95% CI, NR-NR) vs PVd (NR; 95% CI, 42.7 months-NR), with a hazard ratio (HR) of 0.72 (95% CI, 0.20-2.53). BPd LTRs continued to demonstrate potential benefits after the first subsequent therapy, with median PFS2 (95% CI) of NR (NR-NR) in the BPd LTR arm and NR (44.2 months-NR) in the PVd LTR arm (HR, 0.33; 95% CI, 0.07-1.69). LTRs treated with BPd vs PVd had deeper responses: 76% vs 59% had complete response or better (≥ CR), 56% vs 32% had MRD negativity plus ≥ CR overall (73% vs 54% of pts with ≥ CR), and 39% vs 18% had sustained MRD negativity for ≥12 months, respectively. A higher proportion of pts with high-risk cytogenetics (ie, ≥1 of t[4;14], t[14;16], or del[17p13]) treated with BPd vs PVd achieved long-term response (27% vs 11%). The safety profile in LTRs was generally consistent with that previously reported. Conclusions: More than one-third of pts treated with BPd achieved LTR status, representing a 2.5-fold higher rate than with PVd, with similar rates in pts with high-risk cytogenetics; median PFS with BPd remains unreached. These findings suggest that this broadly accessible BCMA-targeted regimen delivers potential durable clinical benefit, characterized by deep and sustained disease-free survival. Clinical trial information: NCT04484623 .