FDA Considers Label Changes for Some Immunotherapies Due to Potential Vision Loss

The FDA is considering adding the risk of ocular inflammatory conditions to labels for 3 immune checkpoint inhibitors due to sight-threatening complications.

The labels that may face changes include Bristol-Myers Squibb’s Yervoy (ipilimumab), Opdivo (nivolumab) and Merck’s Keytruda (pembrolizumab). The 3 labels currently list uveitis, a type of eye inflation, as a potential immune-mediated adverse reaction, but the FDA’s post-marketing reviews have found further complications including retinal detachment and vision loss.

Ocular inflammation resulting in vision loss is also observed in a study that treated metastatic melanoma with ipilimumab. The study involves a patient that was diagnosed with melanoma that continued to progress during treatment. Eventually, he participated in a clinical trial for ipilimumab and received 3mg/kg every 3 weeks for 3 doses.

Following treatment, he experienced adverse side effects including a rash and diarrhea which were treated with supportive therapy, and then headaches that were resolved with steroids. However, 4 months after the initial treatment, the participant experienced acute vision loss in his left eye, followed by visual loss in his right eye after 5 months.

“High dose steroid therapy stabilized the right eye vision but the left eye vision never improved after initial presentation, again supporting a probable vascular cause for the left eye visual loss,” the study noted. “This may or may not have been secondary to an inflammatory/immune-mediated process (ie, local thrombosis related to inflammation/vasculitis).”

Furthermore, the steroids taken by the patient to treat the adverse effects from the ipilimumab treatment caused further complications. The FDA is considering labeling changes to emphasize the risks of these complications.

"Regulatory discussions are ongoing regarding PD-1 pathway blocking antibodies in attempts to improve the consistency and effectiveness of the information regarding immune-mediated ARs provided in the labels,” explained Tralisa Colby, an FDA public affairs specialist, in a statement to Regulatory Focus. “Those labeling changes may include additional characterization of ocular inflammatory conditions; however, the current term, uveitis, should convey the severity and potential ocular complications to oncology physicians."