Single-Agent Belantamab Mafodotin in Patients with Relapsed or Refractory Multiple Myeloma: Final Analysis of the DREAMM-2 Trial

Introduction: Belantamab mafodotin (belamaf) is a first-in-class, B-cell maturation antigen-binding antibody-drug conjugate containing monomethyl auristatin F. Belamaf eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma immune response. In the primary¹ and 13-month follow-up² DREAMM-2 study analyses in patients with RRMM, belamaf monotherapy demonstrated deep and durable responses, with a manageable safety profile. The aim of this report is to analyze the efficacy/safety profile of belamaf using final data from the pivotal DREAMM-2 study.

Methods: DREAMM-2 (NCT03525678) is a Phase 2, 2-arm, open-label study of single-agent belamaf in patients with triple-refractory RRMM who had ≥3 prior therapies and were refractory to an immunomodulatory agent, and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 mAb. Belamaf doses evaluated were 2.5 and 3.4 mg/kg every 3 weeks (Q3W). The primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, ocular symptoms, and health-related quality of life. Eye exams, including a corneal exam and assessment of change in best corrected visual acuity (BCVA), were conducted at baseline and prior to each dose. The GSK Keratopathy and Visual Acuity scale was used for grading ocular events. Recovery was defined as Grade 1 exam findings/no exam findings, and ≤1-line decline in BCVA vs baseline. Ocular symptoms were graded per CTCAE version 4.03. Patients completed patient-reported outcomes questionnaires during treatment at baseline and Q3/6W.

Results: At the cutoff date (31Mar22), the median duration of follow-up for patients randomized to the belamaf 2.5 mg/kg cohort (N=97) was 12.48 months (range 0.1-40.4), and 13.77 (0.1-42.8) months for patients randomized to the 3.4 mg/kg cohort (N=99) (Table). The ORR in the 2.5 mg/kg and 3.4 mg/kg groups was 32% and 35%, respectively; 19% and 24% of patients (58% and 69% of responders) achieved very good partial response (VGPR) or better. Median time to response was 1.5 months (95% CI 1.0, 2.1) in the 2.5 mg/kg cohort and 1.4 months (0.9, 2.1) in the 3.4 mg/kg cohort. The MRD negativity rate of patients with ≥VGPR was 36% and 23% for the 2.5 and 3.4 mg/kg cohorts. Median duration of response was 12.5 and 6.2 months for the 2.5 and 3.4 mg/kg cohorts. Median PFS was 2.8 and 3.9 months. Median Kaplan-Meier estimated OS was 15.3 and 14.0 months. In patients who achieved ≥VGPR, median PFS was 14.0 and 16.8 months for the 2.5 and 3.4 mg/kg cohorts, respectively. In patients who achieved ≥VGPR, estimated OS was 30.7 and 35.5 months. The 3 most common Grade ≥3 adverse events (AEs) were keratopathy, anemia, and thrombocytopenia (Table). AE-related dose reductions occurred in 36% and 44%, dose delays occurred in 54% and 62%, and AE-related permanent discontinuations occurred in 9% and 5% for the 2.5 and 3.4 mg/kg cohorts, respectively; discontinuation due to ocular events was rare (3% in both cohorts). The most commonly reported ocular events in the 2.5 mg/kg cohort included keratopathy (71%), blurred vision (23%), BCVA reduced to 20/50 (21%), and dry eye (15%). BCVA changes and blurred vision were transient; up to 86% of all patients who had experienced blurred vision or worsening BCVA had resolution by the end of follow up. No permanent complete vision loss occurred. Despite changes in BCVA and blurred vision, EORTC-QLQ-C30 data suggest that overall Global Health Status/QoL, Physical and Role functioning, and overall disease symptoms were maintained or improved during treatment.

Conclusions: This final analysis of DREAMM-2 confirms earlier reports^1,2 that single-agent belamaf (2.5 mg/kg and 3.4 mg/kg) results in rapid, deep, durable, and clinically meaningful responses with a manageable safety profile in patients with RRMM. No new safety signals were observed. Dose modification remained effective in resolving ocular events and allowed patients the clinical benefit gained from continuing treatment with belamaf. Patient quality of life was maintained or improved despite changes in ocular symptoms.

1. Lonial S, et al. Lancet Oncol. 2020;21:207-21; 2. Lonial S, et al. Cancer. 2021;127:4198-212.

Funding: GSK (Study 205678). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Nooka:Bristol-Myers Squibb, Janssen, Takeda, Amgen, Adaptive, GlaxoSmithKline, Sanofi, Oncopeptides, Karyophram, SecureBio, and BeyondSprings: Consultancy, Honoraria. Cohen:GSK and Celgene: Other: Personal fees and other association; GlaxoSmithKline, Bristol-Myers Squibb, and Novartis: Research Funding; Janssen, Takeda, Oncopeptides, Kite Pharma, and Seagen Inc: Other: Personal fees. Lee:GSK: Consultancy, Research Funding; Pfizer: Consultancy; Sanofi: Consultancy; Immunitas Therapeutics: Consultancy; Regeneron: Research Funding; Legend Biotech: Consultancy; Genentech: Consultancy; Karyopharm: Consultancy; Monte Rosa Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding; Oncopetides: Consultancy; Amgen: Research Funding; Janssen: Research Funding. Badros:GSK, BMS: Research Funding; Amgen: Consultancy. Suvannasankha:GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Oncology: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Sutro Biopharma: Research Funding; Regeneron: Research Funding. Trudel:Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Janssen, Amgen, GSK, Genentech: Research Funding; Celgene, Amgen GSK: Consultancy. Chari:Celgene, Novartis, Janssen, Pharmacyclics, Amgen, Seattle Genetics and Takeda: Research Funding; Celgene, Novartis, Amgen, Janssen Oncology, Seattle Genetics, Bristol-Myers Squibb, Karyopharm Therapeutics, Genzyme, Oncopeptides, Takeda, Antengene, GlaxoSmithKline and Secura Bio: Consultancy. Libby:Adaptive Biotechnologies: Consultancy. Hultcrantz:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Intellisphere LLC: Consultancy; Amgen, Daichii Sankyo, Cosette, GSK: Research Funding; Curio Science LLC: Consultancy. Kortuem:Janssen: Research Funding; Janssen, BMS, GSK, Abbvie, Pfizer: Consultancy. Richardson:Sanofi: Consultancy; Secura Bio: Consultancy; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; AstraZeneca: Consultancy; Protocol Intelligence: Consultancy; Takeda, Abbvie, GSK, and Celgene: Consultancy; Takeda: Research Funding; Takeda, Celgene, and GSK: Honoraria; Takeda and GSK: Other: Travel expenses from Takeda and GSK; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding. Popat:Roche: Honoraria; BMS: Honoraria; Takeda, AbbVie, GlaxoSmithKline, and Celgene: Consultancy; Takeda: Research Funding; Janssen, Takeda, Celgene, and GSK: Honoraria; Janssen, Takeda, GSK: Other: Travel expenses from Janssen, Takeda, GSK; GSK: Honoraria, Research Funding; Janssen: Honoraria. Sborov:Bioline: Consultancy; Amgen: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Hakim:GSK: Current Employment, Current equity holder in publicly-traded company. Lewis:GSK: Current Employment, Current equity holder in publicly-traded company. Bhushan:GSK: Current Employment, Current equity holder in publicly-traded company. Gorsh:GSK: Current Employment, Current equity holder in publicly-traded company. Gupta:GSK: Current Employment, Current equity holder in publicly-traded company; Stemline-Menarini: Current Employment. Opalinska:GSK: Current Employment, Current equity holder in publicly-traded company. Lonial:Celgene, Janssen, Takeda: Research Funding; Novartis, BMS, GSK, Amgen, Merck, Janssen: Honoraria; AbbVie, Bluebird, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis Pharma, and Takeda.: Consultancy.