Corneal Toxicity Associated With Belantamab Mafodotin Is Not Restricted to the Epithelium: Neuropathy Studied With Confocal Microscopy
Julia Aschauer, Ruth Donner, Jan Lammer, Philipp K. Roberts, Marion Funk, Hermine Agis, Gerald Schmidinger
Abstract
PURPOSEThe purpose of this study was to investigate epithelial and neuronal changes in patients with refractory/relapsed multiple myeloma (RRMM) before/during belantamab mafodotin (belamaf) treatment using confocal microscopy.DESIGNRetrospective case series.METHODSRRMM patients underwent best-corrected visual acuity (BCVA) testing and slitlamp examination/photography, followed by corneal confocal microscopy (CCM), to evaluate the epithelium and subbasal nerve plexus (SNP) to measure corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) before and during belamaf treatment.RESULTSIn 14 eyes of 7 patients (4 female, 68 ± 10 years of age) with complete follow-up (4 ± 2 months), the median BCVA dropped from 20/25 (20/25-20/20) to 20/40 (20/200-20/32) in the worse eye at the end of follow-up. Microcystic epithelial changes and ocular surface disease were demonstrated biomicroscopically. CCM showed “grape-like” hyperreflective spots in the central basal epithelium that changed to polymorphous-structured cysts in the superficial epithelium, with no pathology detected at the(peri-)limbal structures. The baseline, normal SNP morphology with a mean CNFD, CNBD, and CNFL of 20.25 ± 7.06/mm2, 19.49 ± 12.34/mm2, and 11.8 ± 3.74mm/mm2 respectively, showed severe fiber fragmentation during follow-up, and an observed complete loss of the SNP at the end of follow-up in all eyes.CONCLUSIONSThis study is the first to illustrate neurotoxic effects of belamaf on the human cornea. The purpose of this study was to investigate epithelial and neuronal changes in patients with refractory/relapsed multiple myeloma (RRMM) before/during belantamab mafodotin (belamaf) treatment using confocal microscopy. Retrospective case series. RRMM patients underwent best-corrected visual acuity (BCVA) testing and slitlamp examination/photography, followed by corneal confocal microscopy (CCM), to evaluate the epithelium and subbasal nerve plexus (SNP) to measure corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) before and during belamaf treatment. In 14 eyes of 7 patients (4 female, 68 ± 10 years of age) with complete follow-up (4 ± 2 months), the median BCVA dropped from 20/25 (20/25-20/20) to 20/40 (20/200-20/32) in the worse eye at the end of follow-up. Microcystic epithelial changes and ocular surface disease were demonstrated biomicroscopically. CCM showed “grape-like” hyperreflective spots in the central basal epithelium that changed to polymorphous-structured cysts in the superficial epithelium, with no pathology detected at the(peri-)limbal structures. The baseline, normal SNP morphology with a mean CNFD, CNBD, and CNFL of 20.25 ± 7.06/mm2, 19.49 ± 12.34/mm2, and 11.8 ± 3.74mm/mm2 respectively, showed severe fiber fragmentation during follow-up, and an observed complete loss of the SNP at the end of follow-up in all eyes. This study is the first to illustrate neurotoxic effects of belamaf on the human cornea.