March 12, 2022
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death ligand-1 (PD-L1). ICIs harness the host's immune system for anti-tumor activity.
"A wide range of immune-related adverse events (irAEs) have been documented with the increasing use of ICIs," says Lauren A. Dalvin, M.D., Ophthalmology, at Mayo Clinic in Rochester, Minnesota. "Although ophthalmic irAEs are rare, it is vital that ophthalmologists recognize irAEs and understand their treatment, so life-prolonging ICIs can be continued."
Dr. Dalvin and fellow researchers hypothesized that most ophthalmic irAEs can be managed with targeted therapy and should not require cessation of immunotherapy. To investigate, they identified the frequency of ophthalmic irAEs and need for ICI cessation for patients receiving a variety of currently available ICIs.
Researchers reviewed records for patients who received ICI therapy at Mayo Clinic in Minnesota from Jan. 1, 2010, to Feb. 29, 2020. Their study compared demographics, cancer diagnosis, prior ICI therapy, clinical features and outcomes among checkpoint targets, including CTLA-4 (ipilimumab), PD-1 (pembrolizumab and nivolumab), PD-L1 (atezolizumab, avelumab and durvalumab), and combination therapy consisting of ipilimumab and nivolumab. The study results were published in the British Journal of Ophthalmology in 2021.
Results
Of the 996 patients who received ICI therapy, 28 (2.8%) experienced an ophthalmic side effect that came to the attention of an eye care provider. The ICI that most often preceded side effects was pembrolizumab in 12 (43%) patients, followed by nivolumab in six (21%) patients, atezolizumab in four (14%) patients, ipilimumab and nivolumab combination therapy in four (14%) patients, avelumab in one (4%) patient, and ipilimumab in one (4%) patient. "The most frequent ICI preceding adverse effects was pembrolizumab; however, it was also the most commonly prescribed ICI, used by 475 of 996 patients," notes Dr. Dalvin.
The most common side effect was dry eye in 16 (57%) patients, followed by uveitis in four (14%) patients.
Patients with ophthalmic side effects associated with PD-L1 inhibitors had a greater frequency of ocular surface adverse effects. Patients with ophthalmic side effects associated with combination therapy had a higher frequency of hepatitis as a concurrent systemic adverse effect.
Follow-up was available in 13 (46%) patients. The ophthalmic side effects were controlled without discontinuing therapy in 12 (92%) of these patients. ICI cessation was required in one patient with panuveitis. "Most irAEs were either well controlled or resolved with targeted treatment, such as topical, periocular and systemic corticosteroids for inflammatory effects and artificial tears, topical cyclosporine and punctal occlusion for dry eye," notes Dr. Dalvin.
There were no differences between ICI groups in the following:
- Affected eye
- Sex
- Race
- Type of primary cancer
- ICI therapy
- Duration of ICI use prior to presentation with the ocular side effect
- Length of follow-up
- Need for treatment for ophthalmic event
- Treatment outcome
- ICI discontinuation for ophthalmic adverse event
- Frequency of concurrent systemic adverse effects
- Final visual acuity
"Ophthalmic irAEs are rare but could be more common than previously estimated," says Dr. Dalvin. "Our research indicates that most ophthalmic events, however, can be treated with targeted therapy without discontinuation of life-prolonging immunotherapy. It is crucial that ophthalmologists maintain a high index of suspicion for these adverse effects and, if necessary, carefully weigh the risks and benefits of discontinuing life-prolonging therapy in communication with the patient's medical oncologist."
For more information
Fortes BH, et al. Ophthalmic adverse effects of immune checkpoint inhibitors: The Mayo Clinic experience. British Journal of Ophthalmology. 2021;105:1263.
Refer a patient to Mayo Clinic.