Strategies for prevention and management of ocular events occurring with mirvetuximab soravtansine

Abstract

Mirvetuximab soravtansine (MIRV) is a first-in-class antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα) and is indicated for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior systemic treatment regimens. MIRV has demonstrated single-agent anticancer activity in clinical trials, with a differentiated safety profile comprising primarily low-grade, resolvable gastrointestinal and ocular adverse events (AEs). Pooled safety analysis of 464 MIRV-treated patients across 3 trials, including the phase 2 SORAYA study, found that 50% of patients had ≥1 ocular AEs of interest (AEIs) of blurred vision or keratopathy, the majority being grade ≤2. Grade 3 ocular AEIs occurred in 5% of patients, and 1 patient (0.2%) had a grade 4 event of keratopathy. All grade ≥2 AEIs of blurred vision and keratopathy resolved to grade 1 or 0 in patients with complete follow-up data. MIRV-associated ocular AEs were primarily characterized by resolvable changes to the corneal epithelium, with no cases of corneal ulcers or perforations. This reflects the distinctive, milder ocular safety profile for MIRV compared with that of other ADCs with ocular toxicities in clinical use. To maintain a generally low incidence of severe ocular AEs, patients should follow recommendations for maintaining ocular surface health, including daily use of lubricating eye drops and periodic use of corticosteroid eye drops, and should undergo an eye examination at baseline, at every other cycle for the first 8 cycles of treatment, and as clinically indicated. Dose modification guidelines should be followed to maximize patients' ability to remain on therapy. Close collaboration between all care team members, including oncologists and eye care professionals, will help patients benefit from this novel and promising anticancer agent. This review focuses on the etiology, rates, prevention, and management of MIRV-associated ocular events.

Keywords: Antibody-drug conjugates; Eye care; Folate receptor alpha; Mirvetuximab soravtansine; Ocular adverse events; Ovarian cancer.

Fig. 1

Images of Ocular Findings From Case Studies (Kunkler et al., 2019, Corbelli et al., 2019). Case study 1 (A-D): A 56-year-old female with ovarian cancer and normal baseline ocular examination received treatment with MIRV (Kunkler et al., 2019). After 5 weeks of treatment, the patient presented with a complaint related to bilateral vision changes. Slit lamp examination identified bilateral subepithelial corneal microcysts (arrows) (A, B). Corneal topography at 5 weeks showed flattening of the corneal surface curvature (C), with an associated shift in manifest refraction. The patient continued MIRV therapy and was treated with a trial of tobramycin/dexamethasone eye drops, and ocular symptoms improved in 1 week. After 1 month of continued tobramycin/dexamethasone eye drop use, vision symptoms and ocular examination, including corneal topography (D), returned to baseline. Reprinted by permission from the Copyright Clearance Center: Springer Nature Kunkler AL, et al. Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics. Graefe’s Arch Clin Exp Ophthalmol. 2019;257(8):1771-1781. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Case study 2 (E-H): A case series of 5 female patients (median age [range], 62 years [56-71]) treated with MIRV for advanced platinum-resistant EOC were selected based on appearance of ocular symptoms shortly after initiating therapy (Corbelli et al., 2019). The average time of ocular symptom appearance was 4.1 ± 1.7 days. Each patient received complete ophthalmic examinations including AS-OCT, and mean BCVA was between 20/20 and 20/25 at presentation. Ocular events presented as mild (1 patient), moderate (2 patients), and severe (2 patients). Two patients demonstrated a change in manifest refraction (increase in hyperopic astigmatism) in 3 eyes. Bilateral conjunctival hyperemia and fine subepithelial corneal microcysts were observed in all 5 patients by slit lamp examination; these were typically peripherally distributed up to the limbus in a circumferential pattern with anterior migration. Representative slit lamp images from 1 patient show the right eye (E, with magnified view in F) and the left eye (G, with magnified view in H) with small translucent dots, corresponding to corneal microcysts (further identified with asterisks). The subepithelial location of the microcysts was confirmed by AS-OCT. Following treatment with the topical steroid fluorometholone acetate (gradually tapered over a 4- to 6-week period) and daily preservative-free lubricating eye drops, the cornea cleared in all 5 patients and vision symptoms recovered completely. Corbelli E, Miserocchi E, Marchese A, et al. Ocular toxicity of mirvetuximab. Cornea. 2019;38(2):229-232. https://doi.org/10.1097/ICO.0000000000001805. © 2018 Wolters Kluwer Health, Inc. Abbreviations: AS-OCT, anterior segment optical coherence tomography; BCVA, best-corrected visual acuity; EOC, epithelial ovarian cancer; MIRV, mirvetuximab soravtansine.

Fig. 2

Recommendations for Prevention and Management of Ocular Events in Patients Treated With MIRV(Elahere, 2022). Ocular events associated with MIRV should be managed by a combination of patient/caregiver education and preventive steps, as well as management and oversight by the treating oncologist and the entire treatment team, in close collaboration with an ECP (ophthalmologist or optometrist). Abbreviations: BCVA, best-corrected visual acuity; ECP, eye care professional; HCP, healthcare professional; MECs, microcystic-like epithelial changes; MIRV, mirvetuximab soravtansine; PI, prescribing information.