How are ocular toxicities associated with belantamab mafodotin managed in MM?

The Multiple Myeloma Hub was pleased to speak to Hermann Einsele, Julius-Maximilians-Universität Würzburg, DE. We asked, How are ocular toxicities associated with belantamab mafodotin managed in MM? 

In this interview, Einsele discusses the proposed mechanism of belantamab mafodotin-associated ocular toxicity, strategies for monitoring ocular changes, and the role of dose modifications in managing ocular adverse events (AEs) in patients with multiple myeloma (MM). 

Key points 

• Belantamab mafodotin is a first-in-class humanized antibody–drug conjugate (ADC) comprising an anti-B-cell maturation antigen (BCMA) monoclonal antibody, which binds to BCMA expressed on malignant plasma cells, conjugated to the microtubule inhibitor monomethyl auristatin F (MMAF).¹ 
• Belantamab mafodotin eliminates myeloma cells through a number of mechanisms, including induction of apoptosis and immune-mediated responses, and is an effective treatment option for patients with relapsed/refractory MM.^1–3  
• Ocular events have been reported with ADCs across a range of therapeutic targets; ocular AEs are common with belantamab mafodotin and may include dry eye, photophobia, blurred vision, and reduced visual acuity.^4,5  
• The exact mechanisms underlying ocular toxicity are not fully understood, although increasing evidence suggests that off-target uptake of the MMAF cytotoxic payload via macropinocytosis by corneal epithelium cells may lead to microcyst-like epithelial changes.⁵ 
• Belantamab mafodotin-associated ocular toxicities have been shown to be reversible in most patients (92–98%), with recovery occurring through regeneration of the corneal epithelium.^1,6 
• Effective monitoring and management of ocular AEs requires multidisciplinary collaboration between hematology, ophthalmology, and primary care teams.¹ 
• Assessment of ocular toxicities should incorporate baseline and ongoing ophthalmologic examinations, including visual acuity testing, and patient-reported symptoms, including the impact of visual changes on daily activities.^1‒3,7 
• Recommendations for ophthalmologic monitoring differ regionally. The US Prescribing Information specifies examinations at baseline, before every dose, promptly for new or worsening ocular symptoms, and as clinically indicated. In contrast, the EU Summary of Product Characteristics specifies examinations before each of the first four doses and as clinically indicated.^2,3 
• Early identification and reporting of ocular toxicities can facilitate timely intervention and appropriate management to support treatment continuation.^7,8 
• Belantamab mafodotin-associated ocular toxicities can be managed through dose modifications, including dose delays, treatment interruptions, and extending dosing intervals, with decisions guided by the severity of ophthalmic exam findings.^2,3,8 
• In the DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) trials, dose delays occurred in 88% and 93% of patients, respectively, while dose reductions occurred in 69% and 58%, respectively.⁸ 
• Visual impairments were generally reversible following dose modifications, while treatment efficacy was maintained in both trials.⁸ 
• Additional recommendations for the management of ocular AEs include instructing patients not to wear contact lenses, to clean the outer region of the eye, and to wear sunglasses when exposed to sunlight.^1,2,3,9,10 
• Patient counseling should be incorporated into the treatment plan, including discussion of expected visual changes, their potential impact on quality of life, and the reversibility of ocular AEs following dose modifications.^1,7,8 

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