Ocular Toxicity of Belantamab Mafodotin, an Oncological Perspective of Management in Relapsed and Refractory Multiple Myeloma

Abstract

Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.

“Real-life” data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma—the Mayo Clinic experience

“…Belantamab is associated with adverse effects typically seen with other myeloma therapies (such as thrombocytopenia, anemia, and infusion-related reactions) [ 12 ], but also with a unique adverse effect of ocular toxicity [ 13 , 14 ]. Grade 3–4 keratopathy (e.g., corneal epithelium changes) was reported in 46% of the DREAMM-2 cohort [ 12 ].…”

Belantamab Mafodotin-blmf: A Novel Antibody-Drug Conjugate for Treatment of Patients With Relapsed/Refractory Multiple Myeloma

“…The exact mechanism is not well defined, but proposed mechanisms include premature cleavage of the linker in extracellular environments, linker-cytotoxin intracellular metabolism, and Fc-receptor–mediated cellular uptake. This keratopathy may be asymptomatic and only detectable on slit lamp and visual acuity exams; therefore, screening and documentation per a REMS program is required, as detailed in the following section ( Wahab et al, 2021 ). Current management of ocular toxicity includes a multidisciplinary approach and is mainly preventative with the use of dose modifications ( Table 1 ) and lubricating eye drops throughout treatment.…”

Ocular adverse effects of therapeutic biologics

“…Ocular toxicity is dose-dependent and attributed to the drug’s microtubule-disrupting monomethyl auristatin- F (MMAF), which produces an off-target injury to corneal epithelial cells. 90 More than half of the patients in the clinical trials of this drug had at least one of the following side effects: keratopathy, changes in visual acuity, blurry vision, and dry eyes. 90 Photophobia, eye irritation, infective keratitis, ulcerative keratitis were also noted in trials but were less frequent.…”

“… 90 More than half of the patients in the clinical trials of this drug had at least one of the following side effects: keratopathy, changes in visual acuity, blurry vision, and dry eyes. 90 Photophobia, eye irritation, infective keratitis, ulcerative keratitis were also noted in trials but were less frequent.…”