Belantamab Mafodotin (Belamaf) for Relapsed/Refractory Multiple Myeloma (RRMM): A Real-World Observational Study

Introduction: Belamaf, a first-in-class B-cell maturation antigen-targeting antibody-drug conjugate (BCMA ADC) approved for the treatment of RRMM, demonstrated rapid, deep, and durable responses as monotherapy in the DREAMM-2 study (NCT03525678). We analyzed electronic health records (EHRs) of US patients with RRMM to characterize those treated with belamaf, including the occurrence and management of ocular events, and the effectiveness of belamaf in the real-world (RW) setting.

Methods: This retrospective, longitudinal, observational study used de-identified data sourced from the US EHR-derived Flatiron Health Database from 01/01/2011 to 12/31/2021. Eligible patients had a confirmed MM diagnosis, ≥1 record for belamaf administration (first administration=index date), were ≥18 years of age on the index date, had available chart abstraction data for ocular safety and effectiveness outcomes of interest, and did not participate in an interventional clinical trial between MM diagnosis date and index date. Patient characteristics and treatment history were described during the time from MM diagnosis to the index date. The post-index follow-up period spanned from index date to the earliest of start of participation in a clinical trial, end of clinical activity, end of data availability, or death. Prespecified terms for belamaf-related ocular adverse events of special interest (AESI; including keratopathy, blurred vision, dry eye, and keratitis), and physician-reported severity information, if available, were abstracted from patient charts. Additionally, frequency/timing of ophthalmic monitoring visits, persistence with belamaf treatment, reasons for belamaf discontinuation, and clinical effectiveness of belamaf (i.e., overall response rate [ORR], overall survival [OS], and progression-free survival [PFS]) were assessed during the post-index period. Kaplan-Meier methods were used for time-to-event analyses. Ocular AESI information for patients with ≥4 months of follow-up is presented separately, as follow-up time was too short to evaluate the incidence of ocular AESI and associated treatment mitigations for patients receiving their first dose of belamaf close to the data cutoff.

Results: Of the 137 patients included in the study, mean age was 67.9 years, 63.5% were White, and 50.4% were female (Table 1). During a median (interquartile range [IQR]) time between MM diagnosis and index date of 4.8 (3.0-6.7) years, 64.2% had received at least 5 lines of therapy prior to belamaf initiation, and 76.6% were triple-class refractory. The median (IQR) post-index period was 3.1 (1.4-6.0) months. Among patients with ≥4 months of follow-up (57 patients), 71.9% had at least 1 ocular AESI, with keratopathy and blurred vision being the most frequent types (Table 2). Mean (SD) time to first ocular AESI was 44.7 (40.2) days. Most ocular AESIs were managed by therapy hold (58.5%). Among those with a keratopathy event and severity information available (n=25), severity was split between mild (48.0%) and moderate/severe (52.0%) keratopathy, and the predominant action taken was a therapy hold. ORR was 30.2% at 6 months and median PFS was 5.4 months. At 3- and 6-months after starting therapy, 48.1% and 31.3% of patients, respectively, were still on treatment with belamaf (Table 2). Among the 76 (55.5%) patients who eventually discontinued belamaf, reason for discontinuation was reported for 71 patients; the most common reasons were disease progression (33.8%), treatment toxicity (19.7%), and a combination of both (15.5%).

Conclusions: These findings provide important insights into the RW use of belamaf in patients with RRMM. Compared with DREAMM-2, patients in this study were slightly older, had fewer prior lines of therapy, and had a shorter time between MM diagnosis and belamaf treatment initiation. As in DREAMM-2, keratopathy was one of the most common ocular AESIs reported in patients receiving belamaf treatment. ORR in this RW study was also consistent with the DREAMM-2 study (30.2% vs 31%).¹ Overall, patients with RRMM treated with belamaf in the RW setting experienced similar outcomes, including therapy holds to address ocular AESI, consistent with the DREAMM-2 study.

References: 1. Lonial et al. Lancet Oncol. 2020:21(2):207-211

Funding: GSK (study 218905)

Hultcrantz:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen, Daichii Sankyo, Cosette, GSK: Research Funding; Intellisphere LLC: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curio Science LLC: Consultancy. Kleinman:GSK: Consultancy; Triphase Accelerator Corp: Consultancy; Calm Water Therapeutics LLC: Current equity holder in private company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Editas Medicine: Consultancy; Ascidian Therapeutics: Consultancy; Prime Medicine: Consultancy; ONL Therapeutics: Consultancy; Helixmith: Consultancy; AGTC: Consultancy; Emergent BioSolutions: Consultancy. Vij:BMS: Honoraria, Other: Grant support; Sanofi: Honoraria, Other: Grant support; GSK: Honoraria; Beigene: Honoraria; adaptive: Honoraria; oncopetideslegend: Honoraria; Takeda: Honoraria, Other: Grant support; Janssen: Honoraria. Escalante:BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Kotowsky:GSK: Current Employment, Current equity holder in publicly-traded company. Bitetti:GSK: Current Employment, Current equity holder in publicly-traded company. Mackay:GSK: Current Employment, Current equity holder in publicly-traded company. Boytsov:GSK: Current Employment, Current equity holder in publicly-traded company. Camadoo-O'Byrne:GSK: Current Employment, Current equity holder in publicly-traded company. Germain:GSK: Research Funding; Analysis Group: Current Employment. Duh:Merck: Research Funding; Apellis Pharmaceuticals: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding; Blueprint Medicine: Research Funding; Takeda Oncology: Research Funding; Shire: Research Funding; Pharmacyclics: Research Funding; GSK: Research Funding. Laliberté:Groupe d'analyse, Ltée: Other: FL is an employee of Groupe d'analyse, Ltée, a consulting company that has provided paid consulting services to Merck & Co., Inc., which funded the development and conduct of this study; GSK: Research Funding. Mahendran:GSK: Research Funding; Analysis Group: Current Employment. Urosevic:GSK: Research Funding; Analysis Group: Current Employment. Lee:Regeneron: Research Funding; Oncopetides: Consultancy; Sanofi: Consultancy; GSK: Consultancy, Research Funding; Karyopharm: Consultancy; Legend Biotech: Consultancy; Pfizer: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding; Amgen: Research Funding; Janssen: Research Funding; Genentech: Consultancy; Monte Rosa Therapeutics: Consultancy; Immunitas Therapeutics: Consultancy.