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
Year: 2024
Type: conference-abstract
Abstract: 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.
Source: Blood
Authors: Vania Hungria, Marek Hus, Pawel Robak, Vera Zherebtsova, Ana Carolina de Almeida Ribas, Marcelo Pitombeira de Lacerda, Kihyun Kim, Sebastian Grosicki, Irwindeep Sandhu, Christopher Ward, Astrid McKeown, Hena Baig, Jie Ma, Benjamin Lariviere, Benga Kazeem, Lydia Eccersley, Sumita Roy-Ghanta, Joanna Opalinska, Maria Victoria Mateos
Institutions: São Germano Oncologia, Medical University of Lublin, Medical University of Lodz, Botkin Hospital, Universidade da Região de Joinville, Samsung Medical Center, Medical University of Silesia, University of Alberta, Cross Cancer Institute, Royal North Shore Hospital, GlaxoSmithKline (Canada), GlaxoSmithKline (United Kingdom), GlaxoSmithKline (United States), Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405038457