Corneal epithelial microcysts as side effect of belantamab mafodotin: Management and evolution

Abstract

Purpose: Blenrep® (Belantamab mafodotin) is an antibody‐drug conjugate that targets an overexpressed antigen in myeloma plasma cells. This agent has its indication on adults with triple‐class refractory multiple myeloma (MM). The most frequently reported adverse event is the appearance of microcyst‐like epithelial changes in the cornea (MEC), produced by the apoptosis of epithelial cells. Our purpose is to describe these findings and their evolution. Methods: The evaluation of the MM patients treated with Blenrep® is a coordinated labor between ophthalmology and haematology departments. At the beginning of the treatment, a regulated baseline examination including visual acuity (VA) and slit lamp examination is performed and a cold mask and artificial tears are provided. Subsequently examination is repeated every 3 weeks, prior to the administration of the next cycle. The ophthalmological findings determine if the next dose can be administered or if it has to be postponed due to a VA loss. The evolution of three patients undergoing Blenrep® treatment was analysed, using anterior segment photography and OCT. Results: 31–92% of the patients on Blenrep® develop ocular events. In our case, the three patients studied developed epitheliopathy during the follow up. One of them, after 2 months, presented a VA loss due to MEC affecting visual axis that required next dose administration delay following haematologist's recommendation. After that period, the microcysts disappeared and VA was recovered. The other two patients also developed MEC, but did not need modification of the scheme since VA was not affected. Conclusions: Blenrep® has proved to be effective on the treatment of triple‐class refractory MM. Its principal adverse event is the appearance of MEC, which in some cases may impair the VA. This effect is reversible with the disappearance of the microcysts with the corneal epithelial regeneration cycle by prolonging the interval between the doses.

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future

“…However, the most serious toxic effect accompanying the use of this ADC has been the corneal microcyst-like epithelial changes (MECs) first reported in 72% (68/95) of DREAMM-2 patients [76]. This effect, which is not subject to corticosteroid relief but may be reversed by dose reduction [77], has been consistently observed in other studies of not only this but other MMAF-containing ADCs, although its mechanism is unknown [78][79][80][81]. Consequently, the initial FDA approval of belantamab mafodotin was accompanied by a boxed-warning requirement, stating that changes in the corneal epithelium may result in vision loss, corneal ulcers, blurred vision, and dry eyes.…”