Ocular Toxicity Management Is Paramount for Mirvetuximab Soravtansine Treatment

Courtney Arn, APRN-CNP

Nurses caring for patients receiving mirvetuximab soravtansine-gynx (Elahere) must reinforce the importance of adhering to the recommended eye care plan, including eye exams before and during treatment, and instruct patients on the importance of monitoring for ocular symptoms, according to Courtney Arn, APRN-CNP. ¹

Arn, who is a nurse practitioner at The Ohio State University James Cancer Hospital, presented on best practices in ocular toxicity management during the 48th Annual Oncology Nursing Society Congress. In a poster presentation, she explained that preventative and mitigative eye care is necessary to minimize the risk and severity of ocular adverse effects (AEs) that may occur with mirvetuximab soravtansine.

Specifically, patients should receive a baseline ophthalmic exam from an eye care professional prior to starting treatment with mirvetuximab soravtansine, and these eye exams should continue every other treatment cycle. Patients should be instructed on how to maintain eyelid margin hygiene, the importance of wearing sunglasses during daylight hours, and why it necessary to avoid contact lenses (unless otherwise directed) during their treatment.^1,2

Patients undergoing this treatment will also need to apply 1 drop of ophthalmic topical steroids in each eye 6 times daily, beginning on the day before their infusion and continuing until day 4. After day 4, they will need to apply 1 drop in each eye 4 times daily for the remaining days (days 5 to 8) of the treatment cycle. They will also need to use preservative-free lubricating eyedrops at least 4 times daily.

Depending on the severity or persistence of the ocular event, doses may need to be withheld, reduced, or permanently discontinued. In the case of nonconfluent superficial keratitis, grade 1 uveitis, or uveitis in the anterior chamber, no dose reduction action is needed.

The treatment dose should be withheld, and restarted at the same dose level, if the patient experiences confluent superficial keratosis, a cornea epithelial defect, or a loss of at least 3 lines in best corrected visual acuity; or if they experience either grade 1 uveitis or a uveitis flare in the anterior chamber.

If patients develop a corneal ulcer, stromal opacity, or their best corrected visual acuity becomes 20/200 or worse, have either grade 3 uveitis, or a grade 3 flare in the anterior chamber, the dose should be held, and reduced by 1 dose level.

Treatment should be discontinued if the patient develops a corneal perforation, grade 4 uveitis, or grade 4 hypopyon.

According to Arn, nurses must inquire about potential ocular discomfort or pain, dryness of irritation, or changes in visual function, when they meet with patients and encouraging them to contact their health care provider team promptly if any of these symptoms do occur. ¹

“The nursing team plays a vital role in educating patients regarding ocular AEs and their management prior to the initiation of mirvetuximab soravtansine,” she said.

Experience in Clinical Trials

Mirvetuximab soravtansine, an antibody drug conjugate, recently received accelerated approval for patients with folate receptor alpha (Frα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have already undergone between 1 to 3 prior lines of systemic treatments.² The agent is associated with ocular or vision-related adverse events; it is hypothesized that these are related to the drugs cytotoxic payload, DM4, which may exert cytotoxic effects on dividing cells located within the corneal epithelium of the eye, which is believed to disrupt the continuous regeneration of the corneal surface.¹

Data were pooled from 3 clinical trials, hosted out of a total of 15 different countries, in which patients received single agent mirvetuximab soravtansine at a dose of 6 mg/kg every 3 weeks. These trials were the 401 phase 1 trial (NCT0160955), the phase 3 FORWARD trial (NCT02631876), and the phase 2 SORAYA trial (NCT04296890). Combined, the trials included data from 464 patients.

Among patients who were evaluated in this study, the median age was 63 years (range, 34-89). Most patients had epithelial ovarian cancer (84%), a high Frα expression levels (≥ 75% of tumor cells; 67%) and had received at least 3 prior lines of therapy (52%). Regarding prior treatments, 65% had received prior treatment with bevacizumab (Avastin), and 25% had received a PARP inhibitor. Fifty-three percent of patients had received platinum-based chemotherapy as their last systemic treatment before initiating mirvetuximab soravtansine.

Further, at baseline, 22% had cataracts, 13% had dry eye, 7% had blurry vision, 6% had vitreous floaters, and 2% had keratopathy. Throughout the course of treatment, 42%, 26%, and 22% of patients developed any-grade blurred vision, keratopathy, or dry eye, respectively. The incidence rate for grade 3 or worse events were 3%, 3%, and 1%.

In the SORAYA population, specifically (n = 106), the rates of any grade blurred vision, keratopathy, or dry eye were 41%, 29%, and 25%. For grade 3 or worse AEs, the rates were 6%, 9%, and 2%.

Overall, among 464 patients (50%) reported an ocular event throughout treatment, although no corneal ulcers or perforations occurred. Keratopathy and blurred vision were the most common grade 3 or worse TRAEs.

The median time to the first ocular event was 1.2 months (range, 0.02-12.9). Of note, 61% of patients with ovarian cancer experienced an ocular AE, of which more than 90% were grade 1 or 2, 9% were grade 3, and 0.2% were grade 4%. One patient experienced grade 4 keratopathy and was unable to continue with the study. This patient had nonconfluent corneal deposits. These were treated as dry eye syndrome, and both the visual acuity and corneal change resolved completely in 15 days.

In the population of patients who experienced ocular events (n = 231), 57% did not need any dose-related action, 39% needed a dose interruption, 23% needed a dose reduction, and 1% permanently discontinued treatment.

Ultimately, no patients had any permanent ocular sequelae, and of those who did develop and ocular toxicity, 49% had complete resolution, and 39% achieved at least partial improvement.

“Ocular toxicities have been linked to several antibody-drug conjugates, including mirvetuximab soravtansine,” Arn concluded. “Early detection and mitigation may reduce the severity of ocular events and help patients remain on treatment.”

Editor’s Note: Arn reported disclosures with Eisai, Merck, Genmab, Seagen, ImmunoGen, and AztraZeneca.

References

1. Arn C, Riaz KM, Hendershot AJ, Moore KH, O’Malley DM, Lyle K. Strategies for collaborative management of ocular adverse events of mirvetuximab soravtansine patients with folate receptor alpha (Fra)–positive recurrent ovarian cancer. Presented at: 48th Annual Oncology Nursing Society Annual Congress; April 27-May 1, 2022; San Antonio, TX. Accessed April 25, 2023.
2. Elahere. Prescribing information. ImmunoGen, Inc; 2022. Accessed April 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761310s000lbl.pdf