Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial
- PMID: 40680754
- DOI: 10.1016/S1470-2045(25)00330-4
Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial
Abstract
Background: In the primary (first interim) analysis of the DREAMM-7 trial (median follow-up 28·2 months), belantamab mafodotin, bortezomib, and dexamethasone (BVd) showed a statistically significant and clinically meaningful progression-free survival benefit versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM) after at least one line of therapy. The aim of this study is to report overall survival from the second interim analysis, with extended follow-up.
Methods: In the ongoing global, open-label, randomised, phase 3 DREAMM-7 trial done at 142 study centres (research facilities, hospitals, and institutions) in 20 countries across North America, South America, Europe, and the Asia-Pacific region, eligible patients were aged at least 18 years and had confirmed multiple myeloma (according to International Myeloma Working Group criteria), an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and progression on or after at least one previous line of therapy. Patients were randomly assigned (1:1) by use of a central interactive response technology system to receive BVd, which comprised belantamab mafodotin 2·5 mg/kg intravenously every 3 weeks plus bortezomib 1·3 mg/m2 subcutaneously (twice weekly in 21-day cycles, for up to eight cycles) plus dexamethasone 20 mg orally or intravenously (on the day of, and after, bortezomib; for up to eight cycles), or DVd, which comprised daratumumab 16 mg/kg intravenously (21-day cycles; once weekly in cycles 1-3, every 3 weeks in cycles 4-8, and every 4 weeks in cycle 9 and beyond) plus bortezomib and dexamethasone; bortezomib and dexamethasone doses and schedules were the same as those in the BVd group. Randomisation was stratified by number of previous lines of therapy, previous bortezomib, and Revised International Staging System stage. Treatment assignments were unmasked for study personnel and patients; however, they were masked to the independent review committee. Patients received treatment until progressive disease, death, unacceptable toxicity, withdrawal of consent, or loss to follow-up, whichever occurred first. The primary endpoint was progression-free survival; key secondary endpoints were overall survival, minimal residual disease negativity in patients with a complete response or better, duration of response to treatment, and safety. Analysis of efficacy endpoints was based on assessments in all patients who were randomly assigned (ie, the intention-to-treat population). The safety population included all randomly assigned patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04246047, and is ongoing.
Findings: From May 7, 2020, to June 28, 2021, of 623 patients assessed for eligibility, 494 were randomly assigned to receive BVd (n=243) or DVd (n=251); 272 (55%) were male, and 409 (83%) were White. The median age of the patients was 64·5 years (IQR 57·0-71·0). At the updated data cutoff (Oct 7, 2024) and median follow-up (39·4 months [IQR 14·6-42·9]), early, sustained, and significant overall survival benefit was observed with BVd versus DVd. Median overall survival was not reached (NR; 95% CI NR-NR) with BVd and NR (41·0 months-NR) with DVd (hazard ratio [HR] 0·58; 95% CI 0·43-0·79; p=0·0002). BVd versus DVd led to greater than double the minimal residual disease-negativity rates in patients with a complete response or better (25% [95% CI 19·8%-31·0%] vs 10% [6·9%-14·8%]) and median duration of response (40·8 months [95% CI 30·5 months-NR] vs 17·8 months [13·8-23·6]). Analysis of progression-free survival 2 showed that the treatment benefit favouring BVd versus DVd was maintained following subsequent antimyeloma therapy; median progression-free survival 2 was NR with BVd (95% CI 45·6-NR) versus 33·4 months (95% CI 26·7-44·9) with DVd (HR, 0·59; 95% CI, 0·45-0·77). The most common grade 3 or 4 adverse event was thrombocytopenia (135 [56%] of 242 with BVd vs 87 [35%] of 246 with DVd). Serious adverse events occurred in 129 (53%) of 242 patients receiving BVd and 94 (38%) of 246 patients receiving DVd; the most common events were pneumonia (29 [12%] vs 11 [4%]), pyrexia (12 [5%] vs 10 [4%]), and COVID-19 (11 [5%] vs 10 [4%]). Treatment-related serious adverse events that led to death occurred in seven (3%) of 242 patients receiving BVd (pneumonia [n=4], gastrointestinal haemorrhage [n=1], subdural haemorrhage [n=1], or mesenteric vessel thrombosis [n=1]) and two (1%) of 246 receiving DVd (COVID-19 [n=2]).
Interpretation: DREAMM-7 showed significant and clinically meaningful overall survival, progression-free survival, minimal residual disease negativity, and duration of response benefits with BVd versus DVd. BVd could be a new standard of care for RRMM.
Funding: GSK.
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Conflict of interest statement
Declaration of interests VH reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Bristol Myers Squibb (BMS), GSK, Janssen, Sanofi, Pfizer, and Takeda and participation on a data safety monitoring or advisory board for BMS, GSK, Janssen, Kite, Regeneron, and Sanofi. CW reports payment or honoraria for lectures, presentations, and speakers bureaus from AstraZeneca, CSL, GSK, Alexion, Bayer, and Drivetime Radio and was the education and planning committee chair for the ISTH 2024 Congress. PJH reports participation on a data safety monitoring or advisory board for the Australasian Leukaemia & Lymphoma Group trials, unpaid leadership or fiduciary roles in advisory boards for Antengene, Gilead, iTeos Therapeutics, Janssen, and Pfizer, and research and medical writing support from Novartis. RH reports grants or contracts from Amgen, BMS, Celgene, Janssen, Novartis, and Takeda, consulting fees from Amgen, AbbVie, BMS, Celgene, Janssen, Novartis, PharmaMar, and Takeda, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, BMS, Celgene, Janssen, PharmaMar, and Takeda, support for attending meetings or travel from Amgen, Celgene, Janssen, and Takeda, participation on a data safety monitoring or advisory board for Amgen, BMS, GSK, Janssen, Oncopeptides, Sanofi, and Takeda, and stock or stock options in GSK. KK reports consultancy fees from Johnson & Johnson, BMS, AbbVie, and GSK and research funding from Sanofi, Johnson & Johnson, and BMS. IS reports consulting fees and honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen, Celgene, BMS, Pfizer, Sanofi, GSK, FORUS, and BeiGene. CC reports stock or stock options in GSK and advisory board speaker fees from AbbVie, Amgen, Astellas Pharma, BeiGene, BMS, GlycoMimetics, GSK, ImmunoGen, Janssen, Jazz Pharmaceuticals, Karyopharm, Menarini, Stemline Therapeutics, Oncopeptides, Pfizer, Sanofi, Servier, and Takeda. PG has received honoraria for participation on a data safety monitoring board or advisory board for Merck Sharp & Dohme (MSD) and GSK and has accepted an invitation to participate in an advisory board for GSK (New Zealand). MAD reports honoraria for advisory boards and satellite symposia from Amgen, Sanofi, Regeneron, Menarini, Takeda, GSK, BMS, Janssen, BeiGene, Swixx Biopharma, and AstraZeneca. MG reports consulting fees from Janssen, Takeda, Novartis, Amgen, BMS, and GSK, payment or honoraria for a speakers bureau from Janssen, payment or honoraria for lectures from Takeda, Novartis, Amgen, BMS, GSK, and Alnylam, advisory board travel support from Takeda and Novartis, participation on a data safety monitoring board or advisory board for Janssen, Celgene, and Stemline Therapeutics, leadership or fiduciary roles in other board, society, committee, or advocacy groups (paid or unpaid) for Amgen and Sanofi, stock or stock options in GSK, and research support from Janssen. MC reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, BMS, Celgene, GSK, Janssen, Sanofi, Pfizer, Menarini, and Stemline Therapeutics. RRi reports employment with or stock or stock options in McKesson Biosimilar (equity holder in publicly traded company), consulting fees from Amgen, BMS, Takeda, and Fresenius Kabi, and membership on a board of directors or advisory committee for Coherus, Amgen, BMS, Sanofi, Fresenius Kabi, and Takeda. JF, AMa, NP, SV, JL, AMc, RRo, HB, LE, SR-G, PM, and JN report employment with or stock or stock options in GSK. JO reports employment with and/or stock or stock options in GSK and has patents planned, issued, or pending. M-VM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen, BMS, GSK, Sanofi, AbbVie, Kite, Stemline Therapeutics, and Pfizer and participation on a data safety monitoring or advisory board for Janssen, BMS, Amgen, Sanofi, GSK, Roche, Pfizer, AbbVie, Kite, and Stemline Therapeutics. PR, MH, VZ, SG, HS, AB, MPdL, GAM, ASB, CF, A-OA, MEG, AOR, TF, and MM report no other conflicts of interest.
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