Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study - 19/12/19

Doi : 10.1016/S1470-2045(19)30788-0

Sagar Lonial, ProfMD ^a,⁎ , Hans C Lee, MD ^b, Ashraf Badros, ProfMD ^c, Suzanne Trudel, MD ^d, Ajay K Nooka, MD ^a, Ajai Chari, MD ^e, Al-Ola Abdallah, MD ^f, Natalie Callander, ProfMD ^g, Nikoletta Lendvai, MD ^h, Douglas Sborov, MD ⁱ, Attaya Suvannasankha, MD ^j, Katja Weisel, ProfMD ^k,^l, Lionel Karlin, MD ^m, Edward Libby, MD ⁿ, Bertrand Arnulf, MD ^o, Thierry Facon, ProfMD ^p, Cyrille Hulin, MD ^q, K Martin Kortüm, MD ^r, Paula Rodríguez-Otero, MD ^s, Saad Z Usmani, ProfMD ^t, Parameswaran Hari, ProfMD ^u, Rachid Baz, MD ^v, Hang Quach, MD ^w, Philippe Moreau, ProfMD ^x, Peter M Voorhees, MD ^t, Ira Gupta, MD ^y, Axel Hoos, MD ^y, Eric Zhi, PhD ^y, January Baron, MS ^y, Trisha Piontek, BSN ^y, Eric Lewis, MD ^z, Roxanne C Jewell, PhD ^z, Elisha J Dettman, PhD ^y, Rakesh Popat, MD ^aa, Simona Degli Esposti, MD ^ab, Joanna Opalinska, MD ^y, Paul Richardson, ProfMD ^ac, Adam D Cohen, MD ^ad

^a Emory University, Winship Cancer Institute, Atlanta, GA, USA

^b MD Anderson Cancer Center, Houston, TX, USA

^c University of Maryland at Baltimore, Baltimore, MD, USA

^d Princess Margaret Cancer Centre, Toronto, ON, Canada

^e Icahn School of Medicine at Mount Sinai, NY, USA

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

^g University of Wisconsin, Carbone Cancer Center, Madison, WI, USA

^h Memorial Sloan-Kettering Cancer Center, New York City, NY, USA

ⁱ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

^j Indiana University Cancer Center, Indianapolis, IN, USA

^k University Medical Center of Hamburg-Eppendorf, Hamburg, Germany

^l University Hospital of Tuebingen, Tuebingen, Germany

^m Haematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Benite, France

ⁿ Division of Medical Oncology, University of Washington, Seattle, WA, USA

^o Immuno-hématologie, Hôpital Saint-Louis, APHP, Paris, France

^p CHRU de Lille, Hôpital Claude Huriez, Lille, France

^q CHU de Bordeaux, Hôpital Haut Lévêque, Pessac, France

^r Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany

^s Clínica Universidad de Navarra-Pamplona, Navarra, Spain

^t Levine Cancer Institute, Atrium Health, Charlotte, NC, USA

^u Medical College of Wisconsin, Milwaukee, WI, USA

^v Moffitt Cancer Center, Tampa, FL, USA

^w University of Melbourne, St Vincent’s Hospital Melbourne, Melbourne, VIC, Australia

^x CHU de Nantes - Hôtel Dieu Service Hématologie Clinique, Nantes, France

^y GlaxoSmithKline, Philadelphia, PA, USA

^z GlaxoSmithKline, Research Triangle Park, NC, USA

^aa University College London Hospitals, NHS Foundation Trust, London, UK

^ab NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK

^ac Dana-Farber Cancer Institute, Boston, MA, USA

^ad Abramson Cancer Center, Philadelphia, PA, USA

^* Correspondence to: Professor Sagar Lonial, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA Winship Cancer Institute of Emory University Atlanta GA 30322 USA

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Summary

Background

Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study.

Methods

DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with relapsed or refractory multiple myeloma with disease progression after three or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody with an Eastern Cooperative Oncology Group performance status of 0–2 were recruited, centrally randomly assigned (1:1) with permuted blocks (block size 4), and stratified by previous lines of therapy (≤4 vs >4) and cytogenetic features to receive 2·5 mg/kg or 3·4 mg/kg belantamab mafodotin via intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. The intention-to-treat population comprised all randomised patients, regardless of treatment administration. The safety population comprised all patients who received at least one dose of belantamab mafodotin. The primary outcome was the proportion of randomly assigned patients in the intention-to-treat population who achieved an overall response, as assessed by an independent review committee. This study is registered with ClinicalTrials.gov, NCT03525678, and is ongoing.

Findings

Between June 18, 2018, and Jan 2, 2019, 293 patients were screened and 196 were included in the intention-to-treat population (97 in the 2·5 mg/kg cohort and 99 in the 3·4 mg/kg cohort). As of June 21, 2019 (the primary analysis data cutoff date), 30 (31%; 97·5% CI 20·8–42·6) of 97 patients in the 2·5 mg/kg cohort and 34 (34%; 23·9–46·0) of 99 patients in the 3·4 mg/kg cohort achieved an overall response. The most common grade 3–4 adverse events in the safety population were keratopathy (in 26 [27%] of 95 patients in the 2·5 mg/kg cohort and 21 [21%] of 99 patients in the 3·4 mg/kg cohort), thrombocytopenia (19 [20%] and 33 [33%]), and anaemia (19 [20%] and 25 [25%]); 38 (40%) of 95 patients in the 2·5 mg/kg cohort and 47 (47%) of 99 in the 3·4 mg/kg cohort reported serious adverse events. Two deaths were potentially treatment related (one case of sepsis in the 2·5 mg/kg cohort and one case of haemophagocytic lymphohistiocytosis in the 3·4 mg/kg cohort).

Interpretation

Single-agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma.