Ocular toxicity of belantamab mafodotin-based combination regimens in multiple myeloma: A systematic review of phase I-III clinical trials.

Abstract

e19578 Background: Belantamab mafodotin (belamaf) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate approved for relapsed/refractory multiple myeloma (RRMM) in combination with bortezomib and dexamethasone. However, ocular toxicity, manifesting as keratopathy and visual acuity decline, frequently leads to dose delays and treatment discontinuation. We conducted a systematic review to summarize the incidence, severity, reversibility, and clinical impact of ocular toxicity associated with belamaf-based combination regimens in multiple myeloma. Methods: PubMed, Embase, Cochrane, and major conference proceedings (ASCO, ASH) were searched through January 2026 to identify interventional trials evaluating belamaf-based combination regimens in multiple myeloma. Eligible phase I–III trials reporting ocular adverse events (OAEs) using trial-defined grading systems, such as the Keratopathy and Visual Acuity (KVA) scale, were included. Monotherapy trials were excluded. Given heterogeneity in regimens, dosing schedules, and outcome definitions, results were summarized descriptively. Results: Six belamaf-based combination trials (n = 689) met the inclusion criteria, including four RRMM studies (DREAMM-7, DREAMM-8, DREAMM-6, ALGONQUIN) and two newly diagnosed multiple myeloma (NDMM) studies (DREAMM-9, BelaRd). In the phase III RRMM trials DREAMM-7 and DREAMM-8, which used standard every-3-week dosing, KVA-assessed OAEs occurred in 84–87% of patients, with grade ≥3 OAEs in 70–74%. Approximately one-third of patients experienced a decline in vision to 20/50 or worse, though severe vision loss (20/200 or worse) was rare, affecting 1–2% of participants. Ocular toxicity was largely reversible, with improvement in 92–98% of patients and median resolution within 9–12 weeks. Treatment discontinuation due to ocular toxicity occurred in 9–10% of patients. Phase I/II RRMM combination studies demonstrated similar toxicity patterns with standard dosing. In contrast, NDMM phase I/II trials explored alternative dosing strategies. In the DREAMM-9 trial, grade ≥3 OAEs occurred in 53% of patients, with dose delays in 52% and dose reductions in 12%. In the BelaRd study, extended-interval dosing (every 8–12 weeks at 1.9 mg/kg) was associated with lower ocular toxicity, with grade 3–4 OAEs in 13.5% of ophthalmologic assessments, grade 3–4 keratopathy in 0.4%, and median resolution within 1–2 months. Conclusions: Ocular toxicity with belamaf-based combination regimens is common in RRMM but is largely reversible and infrequently leads to permanent treatment discontinuation. Early NDMM studies suggest that extended-interval and lower-intensity dosing may reduce ocular toxicity while maintaining clinical benefit. Further prospective research is needed to evaluate the ocular safety of belamaf in earlier-line myeloma settings.