Efficacy Outcomes By Minimal Residual Disease (MRD) Negativity in Patients with Relapsed or Refractory Multiple Myeloma Treated with Belantamab Mafodotin Plus Bortezomib and Dexamethasone Vs Daratumumab, Bortezomib, and Dexamethasone: Analysis from the Dreamm-7 Trial

Background: In DREAMM-7 (NCT04246047), belantamab mafodotin (belamaf) plus bortezomib and dexamethasone (BVd) demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit vs the standard-of-care triplet daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma who had received ≥1 prior line of treatment. MRD negativity has been shown to be a predictor of PFS and overall survival (OS) in multiple myeloma. Here, we aimed to understand if MRD negativity translated to improvements in PFS and OS in the DREAMM-7 trial.

Methods: In DREAMM-7,patients with ≥1 prior line of treatment were randomized (1:1) to BVd or DVd. The primary endpoint was independent review committee (IRC)-assessed PFS. OS and aMRD negative status by next-generation sequencing with 10^-5 sensitivity; follow-up testing was performed every 6 months thereafter until progressive disease. An exploratory MRD analysis was also performed in patients who achieved a very good partial response or better (≥VGPR). Post hoc subgroup analyses of PFS (IRC assessed) and OS were performed based on IRC-assessed response (≥CR or ≥ VGPR) and MRD- negative status and evaluated using the Kaplan-Meier method; CIs were estimated using the Brookmeyer-Crowley method.

Results: In total, 494 patients (BVd, n=243; DVd, n=251) were randomized in the intention-to-treat population. As previously reported, at the first interim analysis (data cutoff: October 2, 2023; median follow-up, 28.2 months), a higher proportion of patients in the BVd arm had CR-based MRD-negative status vs the DVd arm (60 of 243 [25%] vs 24 of 251 [10%] patients). A higher proportion of patients achieved sustained MRD negativity for ≥12 months (≥CR) with BVd (10%) vs DVd (2%) by the data cutoff. Rates of CR-based MRD negativity favored BVd vs DVd in prespecified subgroups of patients with disease refractory to lenalidomide (25% vs 6%) and patients with ≥1 high-risk cytogenetic abnormality (31% vs 7%); this is consistent with findings from the intention-to-treat analysis. A similar trend was observed in an exploratory analysis of patients with ≥VGPR, with 94 of 243 (39%) patients achieving VGPR-based MRD negativity in the BVd arm vs 43 of 251 (17%) patients in the DVd arm.

Inability to achieve MRD-negative status was associated with lower PFS and OS outcomes compared with the intention-to-treat population. Among patients who did not achieve CR-based MRD negativity, median PFS was 15.3 months (95% CI, 12.7-18.0 months; BVd, 25.0 months; DVd, 11.8 months), with an 18-month PFS rate of 45% (95% CI, 40%-50%; BVd, 57%; DVd, 36%); median OS was not reached at the data cutoff, and the 18-month OS rate was 74% (95% CI, 69%-78%; BVd, 79%; DVd, 70%). In patients who achieved CR-based MRD-negative status, median PFS and OS were not reached; by the data cutoff, 13% (BVd, 10%; DVd, 21%) of patients had PFS events, and 5% (BVd, 5%; DVd, 4%) had OS events.

Conclusions: In the DREAMM-7 trial, patients in the BVd arm achieved MRD-negative status at more than double the rate observed in the DVd arm, and more patients achieved sustained MRD-negative status for ≥12 months with BVd. MRD negativity was associated with durable PFS and OS benefits, which is consistent with previous reports; this highlights the importance of the greater response depth that is achieved with BVd.

Funding statement: GSK (Study # 207503)

Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Hungria:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer and Regeneron: Honoraria, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hus:GSK: Honoraria; AbbVie: Honoraria; Johnson & Johnson - Janssen: Honoraria; AMGEN: Honoraria; Novartis: Honoraria; Bristol Myers Squibb - Celgene: Honoraria; Bristol Myers Squibb: Honoraria; MSD: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Eli Lily: Honoraria. Sandhu:GSK: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol-Myers Squibb - Celgene: Consultancy, Honoraria; Johnson & Johnson - Janssen: Consultancy, Honoraria. Ward:Astra-Zeneca: Honoraria, Speakers Bureau; Bayer: Honoraria, Speakers Bureau; Drivetime Radio: Other: Moderators fees for podcast recording; International Society of Thrombosis and Haemostasis: Other: Education Chair. McKeown:GSK: Current Employment, Current holder of stock options in a privately-held company. Baig:GSK: Current Employment, Current holder of stock options in a privately-held company. Ma:GSK: Current Employment, Current equity holder in publicly-traded company. Kazeem:GSK: Current Employment, Current equity holder in publicly-traded company. Eccersley:GSK: Current Employment, Current holder of stock options in a privately-held company. Roy-Ghanta:GSK: Current Employment, Current holder of stock options in a privately-held company. Opalinska:GSK: Current Employment, Current holder of stock options in a privately-held company. Mateos:Amgen, Takeda, Regeneron: Honoraria; BMS/Celgene, Janssen-Cilag, Sanofi, Abbvie, Stemline, Oncopeptides, GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees.