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.

Christchurch Hospital Christchurch New Zealand

Clinica São Germano São Paulo Brazil

Cross Cancer Institute Edmonton AB Canada

Department of Haematology Hadassah Medical Center Faculty of Medicine Hebrew University of Jerusalem Jerusalem Israel

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Gorodskaya Klinicheskaya Bol'nitsa Im Sp Botkina Moscow Russia

GSK Chicago IL USA

GSK Collegeville PA USA

GSK London UK

GSK Mississauga ON Canada

GSK Stevenage UK

Hematology Unit Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST IRCCS Meldola Forlì Cesena Italy

Hospital das Clínicas and Instituto do Câncer do Estado de São Paulo Universidade de São Paulo São Paulo Brazil

Institut Català d'Oncologia and Josep Carreras Research Institute Hospital Germans Trias i Pujol Badalona Spain

Institut Català d'Oncologia L'Hospitalet L Barcelona Barcelona Spain

Instituto de Investigación Biomédica de Salamanca Hospital Universitario de Salamanca IBSAL CIC Ciberonc Salamanca Spain

Liverpool Hospital Sydney NSW Australia

Matsuyama Red Cross Hospital Matsuyama Japan

Medical University of Łódź Łódź Poland

Medical University of Silesia Katowice Poland

Pindara Private Hospital Gold Coast QLD Australia

Rocky Mountain Cancer Centers Denver Midtown Denver CO USA

Royal North Shore Hospital Sydney NSW Australia

Royal Prince Alfred Hospital Camperdown NSW Australia

Samodzielny Publiczny Szpital Kliniczny Lublin Poland

School of Medicine National and Kapodistrian University of Athens Athens Greece; Korea University Seoul South Korea

Sungkyunkwan University Samsung Medical Center Seoul South Korea

The 1st Affiliated Hospital of Soochow University Jiangsu China

Universidade da Região de Joinville and Centro de Hematologia e Oncologia Joinville Santa Catarina Brazil

University Hospital Ostrava and University of Ostrava Ostrava Czech Republic

University Hospitals of Leicester NHS Trust Leicester UK

University of Kansas Cancer Center Fairway KS USA

Lancet Oncol. 2025 Oct;26(10):e522. doi: 10.1016/S1470-2045(25)00488-7. PubMed

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ClinicalTrials.gov
NCT04246047