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

• Published in: Blood 2024-11, Vol.144, p.3359-3359
• Main Authors: Hungria, Vania, Hus, Marek, Robak, Pawel, Zherebtsova, Vera, Ribas, Ana Carolina de Almeida, Lacerda, Marcelo Pitombeira de, Kim, Kihyun, Grosicki, Sebastian, Sandhu, Irwindeep, Ward, Christopher, McKeown, Astrid, Baig, Hena, Ma, Jie, Lariviere, Benjamin, Kazeem, Benga, Eccersley, Lydia, Roy-Ghanta, Sumita, Opalinska, Joanna, Mateos, Maria Victoria
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-201543

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