TY - JOUR
T1 - Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2)
T2 - a two-arm, randomised, open-label, phase 2 study
AU - Lonial, Sagar
AU - Lee, Hans C.
AU - Badros, Ashraf
AU - Trudel, Suzanne
AU - Nooka, Ajay K.
AU - Chari, Ajai
AU - Abdallah, Al Ola
AU - Callander, Natalie
AU - Lendvai, Nikoletta
AU - Sborov, Douglas
AU - Suvannasankha, Attaya
AU - Weisel, Katja
AU - Karlin, Lionel
AU - Libby, Edward
AU - Arnulf, Bertrand
AU - Facon, Thierry
AU - Hulin, Cyrille
AU - Kortüm, K. Martin
AU - Rodríguez-Otero, Paula
AU - Usmani, Saad Z.
AU - Hari, Parameswaran
AU - Baz, Rachid
AU - Quach, Hang
AU - Moreau, Philippe
AU - Voorhees, Peter M.
AU - Gupta, Ira
AU - Hoos, Axel
AU - Zhi, Eric
AU - Baron, January
AU - Piontek, Trisha
AU - Lewis, Eric
AU - Jewell, Roxanne C.
AU - Dettman, Elisha J.
AU - Popat, Rakesh
AU - Esposti, Simona Degli
AU - Opalinska, Joanna
AU - Richardson, Paul
AU - Cohen, Adam D.
N1 - Funding Information:
This study was funded by GlaxoSmithKline. GlaxoSmithKline contributed to study design, implementation, data collection, interpretation and analysis. Medical writing support was funded by GlaxoSmithKline. We thank the ophthalmology and optometry colleagues who provide ophthalmic examinations to patients enrolled in the study, and Jeff Jackson, Karrie Wang, Joe Kovach, Kaytlyn Nungesser, and Alessandra Tosolini. Medical writing support was provided by Fiona Woodward, Chloe Stevenson, and Sarah Hauze, of Fishawack Indicia, UK, funded by GlaxoSmithKline. Drug linker technology was licensed from Seattle Genetics (Bothell, WA, USA) and the monoclonal antibody was produced with POTELLIGENT Technology licensed from BioWa (Princeton, NJ, USA). RP is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and this trial was supported in part by the NIHR UCLH Clinical Research Facility and the Cancer Research UK Experimental Cancer Medicine Centre.
Funding Information:
This study was funded by GlaxoSmithKline. GlaxoSmithKline contributed to study design, implementation, data collection, interpretation and analysis. Medical writing support was funded by GlaxoSmithKline. We thank the ophthalmology and optometry colleagues who provide ophthalmic examinations to patients enrolled in the study, and Jeff Jackson, Karrie Wang, Joe Kovach, Kaytlyn Nungesser, and Alessandra Tosolini. Medical writing support was provided by Fiona Woodward, Chloe Stevenson, and Sarah Hauze, of Fishawack Indicia, UK, funded by GlaxoSmithKline. Drug linker technology was licensed from Seattle Genetics (Bothell, WA, USA) and the monoclonal antibody was produced with POTELLIGENT Technology licensed from BioWa (Princeton, NJ, USA). RP is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and this trial was supported in part by the NIHR UCLH Clinical Research Facility and the Cancer Research UK Experimental Cancer Medicine Centre.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/2
Y1 - 2020/2
N2 - 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. Funding: GlaxoSmithKline.
AB - 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. Funding: GlaxoSmithKline.
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U2 - 10.1016/S1470-2045(19)30788-0
DO - 10.1016/S1470-2045(19)30788-0
M3 - Article
C2 - 31859245
AN - SCOPUS:85078479667
SN - 1470-2045
VL - 21
SP - 207
EP - 221
JO - The lancet oncology
JF - The lancet oncology
IS - 2
ER -