Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study

• Main Authors: Asim V. Farooq, Simona Degli Esposti, Rakesh Popat, Praneetha Thulasi, Sagar Lonial, Ajay K. Nooka, Andrzej Jakubowiak, Douglas Sborov, Brian E. Zaugg, Ashraf Z. Badros, Bennie H. Jeng, Natalie S. Callander, Joanna Opalinska, January Baron, Trisha Piontek, Julie Byrne, Ira Gupta, Kathryn Colby
• Format: Article
• Language: English
• Published: Adis, Springer Healthcare 2020-07-01
• Series: Ophthalmology and Therapy
• Subjects: Antibody–drug conjugate; Belantamab mafodotin; Cornea; In vivo confocal microscopy; Microcyst-like epithelial changes; Monomethyl auristatin F
• Online Access: https://doi.org/10.1007/s40123-020-00280-8

Abstract Introduction Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody–drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. Methods Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. Results In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. Conclusion Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. Trial Registration ClinicalTrials.gov Identifier, NCT03525678.