Long-term responders from the Phase 3 dreamm-7 study of belantamab mafodotin plus bortezomib and dexamethasone vs daratumumab plus bortezomib and dexamethasone in Relapsed/Refractory multiple myeloma Free

Introduction: In the phase 3, open-label, randomized DREAMM-7 trial (NCT04246047) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who had ≥1 prior line of treatment, belantamab mafodotin, bortezomib, and dexamethasone (BVd) led to statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefit vs daratumumab, bortezomib, and dexamethasone (DVd), as well as deep and durable responses after extended follow-up (data cutoff: October 7, 2024; median follow-up, 39.4 months in the intention-to-treat population). This post hoc analysis was conducted to further investigate the characteristics of and outcomes in pts achieving sustained clinical benefit with BVd (ie, long-term responders [LTRs]).

Methods: As previously reported,pts were randomized 1:1 to BVd or DVd. Pts were treated until disease progression, death, unacceptable toxicity, withdrawal of consent, or loss to follow-up, whichever occurred first. The primary endpoint was PFS; key secondary endpoints included duration of response (DOR), minimal residual disease (MRD) negativity, and OS. Other secondary endpoints included response rates, PFS2, and safety. LTRs were defined as pts who had PFS ≥36 months. The last pt was randomized on June 28, 2021; with a data cutoff of October 7, 2024, all pts remaining on study have been on for >3 years.

Results: Of 494 pts in DREAMM-7 (BVd, n=243; DVd, n=251), 125 were LTRs; the BVd arm had approximately twice as many LTRs (n=78 [32%]) as the DVd arm (n=47 [19%]). While baseline characteristics between treatment arms were generally well balanced, LTRs had slightly different baseline characteristics compared with non-LTRs. While all LTRs had Revised International Staging System (R-ISS) stage I or II disease, non-LTRs included a small number of pts with R-ISS stage III disease (n=23 [6%]). Non-LTRs had a 7% higher rate of extramedullary disease vs LTRs. LTRs had fewer prior lines of therapy vs non-LTRs, with 83% vs 71% having 1 or 2 prior lines of therapy, respectively. High-risk cytogenetics were balanced between LTRs and non-LTRs; however, 1q21 amplification was more common in non-LTRs (39%) vs LTRs (24%). In BVd-treated LTRs, median PFS, DOR, PFS2, and OS were not reached (NR). In DVd-treated LTRs, median PFS was 49 months (95% CI, not evaluable [NE]-NE) and median DOR was 48 months (95% CI, NE-NE); median PFS2 and OS were both NR. While all LTRs had a response, LTRs treated with BVd vs DVd had deeper responses: 72% vs 57% had complete response or better (≥ CR), 96% vs 92% had very good partial response or better (≥ VGPR), 54% vs 40% had MRD negativity plus ≥ CR (75% vs 70% of pts with ≥ CR), and 71% vs 53% had MRD negativity plus ≥ VGPR (73% vs 58% of pts with ≥ VGPR), respectively. The safety profile in LTRs who received long-term treatment was consistent with that previously reported.

Conclusions: BVd-treated LTRs had higher rates of ≥ CR and MRD negativity than DVd-treated LTRs, which corresponded with BVd-treated LTRs having longer PFS and more durable responses compared with DVd-treated LTRs. Together, these results further support that deeper responses with BVd resulted in prolonged remission. The safety profile in LTRs was consistent with that previously reported.

Funding statement: GSK (Study ID: 207503).Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.