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 - 16/07/25

Doi : 10.1016/S1470-2045(25)00330-4

Vania Hungria, MD ^a, Paweł Robak, ProfMD ^b, Marek Hus, ProfMD ^c, Vera Zherebtsova, MD ^d, Christopher Ward, ProfMD ^e, P Joy Ho, ProfMBBS ^f, Roman Hájek, ProfMD ^g, Kihyun Kim, ProfMD ^h, Sebastian Grosicki, ProfMD ⁱ, Hanlon Sia, MBBS ^j, Adam Bryant, PhD ^k, Marcelo Pitombeira de Lacerda, ProfMD ^l, Gracia Aparecida Martinez, MD ^m, Anna Sureda Balarí, MD ⁿ, Irwindeep Sandhu, MD ^o, Claudio Cerchione, MD ^p, Peter Ganly, PhD ^q, Meletios A Dimopoulos, ProfMD ^r,^s, Chengcheng Fu, ProfMD ^t, Mamta Garg, MD ^u, Al-Ola Abdallah, MD ^v, Moshe E Gatt, MD ^w, Albert Oriol Rocafiguera, MD ^x, Michele Cavo, ProfMD ^y, Robert Rifkin, MD ^z, Tomoaki Fujisaki, MD ^aa, Michał Mielnik, MD ^c, Joseph Ficek, PhD ^ab, Alejandro Mantero, PhD ^ab, Nick Pirooz, MHA ^ab, Sybil Varghese, MBBS ^ab, Joe Lee, PhD ^ac, Astrid McKeown, PhD ^ad, Rachel Rogers, MS ^ab, Hena Baig, BS ^ae, Lydia Eccersley, PhD ^ac, Sumita Roy-Ghanta, MD ^ab, Pralay Mukhopadhyay, PhD ^ab, Jacqueline Nielsen, PhD ^af, Joanna Opalinska, MD ^ab, María-Victoria Mateos, MD ^ag,⁎
on behalf of the
DREAMM-7 study investigators^{^†}
Study investigators are listed in the appendix

^a Clinica São Germano, São Paulo, Brazil

^b Medical University of Łódź, Łódź, Poland

^c Samodzielny Publiczny Szpital Kliniczny, Lublin, Poland

^d Gorodskaya Klinicheskaya Bol’nitsa Im Sp Botkina, Moscow, Russia

^e Royal North Shore Hospital, Sydney, NSW, Australia

^f Royal Prince Alfred Hospital, Camperdown, NSW, Australia

^g University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic

^h Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea

ⁱ Medical University of Silesia, Katowice, Poland

^j Pindara Private Hospital, Gold Coast, QLD, Australia

^k Liverpool Hospital, Sydney, NSW, Australia

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

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

ⁿ Institut Català d’Oncologia-L’Hospitalet L.-Barcelona, Barcelona, Spain

^o Cross Cancer Institute, Edmonton, AB, Canada

^p Hematology Unit, Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” - IRST IRCCS, Meldola, Forlì-Cesena, Italy

^q Christchurch Hospital, Christchurch, New Zealand

^r School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

^s Korea University, Seoul, South Korea

^t The First Affiliated Hospital of Soochow University, Jiangsu, China

^u University Hospitals of Leicester NHS Trust, Leicester, UK

^v University of Kansas Cancer Center, Fairway, KS, USA

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

^x Institut Català d’Oncologia and Josep Carreras Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain

^y Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

^z Rocky Mountain Cancer Centers—Denver—Midtown, Denver, CO, USA

^aa Matsuyama Red Cross Hospital, Matsuyama, Japan

^ab GSK, Collegeville, PA, USA

^ac GSK, London, UK

^ad GSK, Stevenage, UK

^ae GSK, Mississauga, ON, Canada

^af GSK, Chicago, IL, USA

^ag Instituto de Investigación Biomédica de Salamanca, Hospital Universitario de Salamanca–IBSAL–CIC–Ciberonc, Salamanca, Spain

^* Correspondence to: Dr María-Victoria Mateos, Hospital Universitario de Salamanca/IBSAL/CIC/Ciberonc, Salamanca, 37007, Spain Hospital Universitario de Salamanca/IBSAL/CIC/Ciberonc Salamanca 37007 Spain

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Summary

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.