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    Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    Category: Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    A Network Meta-Analysis of Belantamab Mafodotin + Bortezomib + Dexamethasone vs Alternative Regimens in 2L+ Relapsed/Refractory Multiple Myeloma: Updated Efficacy Outcomes of DREAMM-7

    (PA-499) A Network Meta-Analysis of Belantamab Mafodotin + Bortezomib + Dexamethasone vs Alternative Regimens in 2L+ Relapsed/Refractory Multiple Myeloma: Updated Efficacy Outcomes of DREAMM-7

    Wednesday, September 17, 2025
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    Introduction: The Phase 3 DREAMM-7 trial (NCT04246047) recently reported a significant overall survival (OS) benefit with belantamab mafodotin, an antibody drug conjugate targeting B-cell maturation antigen, in combination with bortezomib and dexamethasone (BVd) vs daratumumab plus bortezomib and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM) who had received ³1 prior line of treatment (2L+; 42% reduction in risk of death; hazard ratio [HR] 95% confidence interval [95% CI]: 0.58 [0.43–0.79]; p=0.00023). Based on the recent efficacy outcomes in the DREAMM-7 trial and emergent results for alternative regimens, it is important to re-evaluate the relative efficacy of BVd compared with other regimens in early RRMM. Here we reported an updated network meta-analysis (NMA) with the DREAMM-7 BVd regimen (median follow-up: 39.4 months).

    Methods: Randomized controlled trials (RCTs) of adults with 2L+ RRMM who progressed on/after most recent therapy were identified in a systematic literature review (Jan 2008–Jan 2024). RCTs were included if they evaluated PFS, OS, or ORR in a regimen approved/likely to be approved by the US Food and Drug Administration/European Medicines Agency or were of interest for health technology assessment. Trials were linked together by the treatment(s) they shared to form connected networks of evidence for each outcome, and a Bayesian NMA was conducted.

    Results: The connected evidence networks comprised 13 RCTs (including DREAMM-7) for PFS, ORR, and OS. All regimens compared to BVd included a proteasome inhibitor (PI) and were: cyclophosphamide (Cy)+Vd (CyVd), Cy + carfilzomib (K)+d (CyKd), DVd, elotuzumab (E)+Vd (EVd), D+K+d (DKd), isatuximab (Isa)+Kd (IsaKd), panobinostat (Pano)+Vd (PanoVd), pomalidomide (P)+Vd (PVd), selinexor (S)+Vd (SVd), Kd, and Vd. PFS of BVd remained the longest of all therapies included in the fixed-effect NMA, with HRs of 0.15–0.48 and all credible intervals (CrIs) did not cross 1, indicating a high probability that the treatment effect was consistently in favor of BVd. Notable PFS HRs (95% CrI) included 0.43 (0.27–0.68) vs DKd, 0.48 (0.29–0.77) vs IsaKd, and 0.46 (0.35–0.60) vs DVd. OS remained longer for BVd than the other regimens, with HRs of 0.40–0.68, and 95% CrIs that did not cross 1 except for 5 comparisons (BVd vs CyVd, EVd, DKd, IsaKd, and Kd). OS HRs (95% CrI) for noteworthy regimens included 0.68 (0.41–1.11) vs DKd, 0.68 (0.39–1.18) vs IsaKd, and 0.58 (0.43–0.78) vs DVd. Odds ratios for ORR favored BVd over the other regimens (range: 1.14–7.60) with 95% CrIs that crossed 1 for 5 regimens (CyKd, DKd, IsaKd, Kd, and PVd).

    Conclusions: Based on updated analyses, the DREAMM-7 BVd regimen continues to demonstrate superior PFS against all comparators, and additionally superior OS and ORR against most comparator PI-based regimens for 2L+ RRMM in the absence of direct RCTs.

    Funding: GSK (214943)