Objective: Single-agent belamaf (GSK2857916), an antibody-drug conjugate (ADC) targeting B-cell maturation antigen, induced clinically meaningful, deep and durable responses in patients with RRMM (DREAMM-2; NCT03525678, Lonial ASCO, 2020). Corneal events were common during belamaf treatment, as with other ADCs. This methodology will establish meaningful, within-individual change in two vision-related PRO instruments, National Eye Institute Visual Functioning Questionnaire-25 item (NEI-VFQ-25) and Ocular Surface Disease Index (OSDI) questionnaires, in the novel context of treatment-related corneal events in patients with RRMM receiving belamaf.

Methods: In DREAMM-2, patients with heavily pre-treated RRMM completed PRO questionnaires every 3 weeks during treatment. A targeted literature review identified publications supportive of NEI-VFQ-25 or OSDI score interpretation and assessment of drug-related corneal events. Clinical anchors were selected using statistical analysis and ophthalmologist input.

Results: Eleven publications supporting NEI-VFQ-25 and OSDI measures were identified. Interpretation guidelines suggested change in values for ocular conditions in which treatment efficacy was evaluated. Twelve publications described assessment of drug-related toxicities with these measures; no articles described meaningful change thresholds.

Anchors were selected for the meaningful change evaluation based on ophthalmologist consultation and review of Spearman correlation coefficients. Ocular PROs changes were examined by pre-defined anchor groupings. Receiver-operating characteristic curves, empirical cumulative distribution functions, and probability density functions of PRO changes were plotted according to anchor groupings, supplemented by distribution-based methods. Triangulated results, based on combined analyses, defined reference values (with reasonable ranges) for clinically meaningful within-individual PRO score changes.

Conclusion: The methodology for this study utilises recommended methods for establishing meaningful change thresholds for ocular PROs measuring treatment-related corneal events in patients with RRMM receiving belamaf. Results will also support the interpretation of these measures for future oncology trials where corneal events may occur.

Funding: GlaxoSmithKline (213290). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.