Clinical Update on Checkpoint Inhibitor Therapy for Conjunctival and Eyelid Melanoma.

Melanomas of the conjunctiva and eyelid present unique management challenges for the ophthalmologist and ocular oncologist. Surgical excision, a mainstay of treatment, may be disfiguring with variable rates of local recurrence.1 Conjunctival melanomas have a local recurrence rate ranging from 18% to 83% with data largely coming from patients treated with excision with or without cryotherapy.2–4 Cutaneous melanomas of the eyelid skin have a local recurrence rate ranging from 7% to 78% depending on technique and extent of excision.5–7 The rate of regional lymph node metastasis was 41% in a study of conjunctival melanoma patients treated primarily with local excision, the authors compared their finding to rates in cutaneous melanoma of the head and neck which ranged from 14% to 44% or eyelid skin melanoma at 29%.4 Efforts to improve outcomes of these tumors have continually advanced with surgical techniques and adjunctive treatments such as topical therapy, radiation, and systemic chemotherapy.8 Recent advances in immunotherapy, specifically checkpoint inhibitors, has allowed for primary and adjuvant treatment of cutaneous melanomas with medical therapy. These have been successful in the setting of metastatic cutaneous melanoma and other cancers. This review of the literature summarizes the current understanding and use of checkpoint inhibitors, with a particular focus for the ophthalmic surgeon. Immune checkpoint inhibitors are relatively new therapies, developed with the rationale of stimulating a patient’s own immune system to better respond to malignancies. This strategy progressed from the discovery of specific receptor proteins that promote immune tolerance, that is, inhibit immune responsiveness, which tumors may take advantage of to proliferate unhindered. Monoclonal antibodies were developed to block these cellular checkpoints. Clinically available therapies include ipilimumab, which targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), nivolumab, pembrolizumab, and cemiplimab, which target programmed cell death-1 (PD-1), and atezolizumab, avelumab, and durvalumab, which target programmed cell death ligand-1 (PD-L1). Checkpoint inhibitors have demonstrated efficacy in a range of malignancies including non–small cell lung cancer, urothelial cancer, renal cell cancer, squamous cell carcinoma of the head and neck, Merkel cell carcinoma, and metastatic cutaneous melanoma.9 In recent years there has been emerging interest in checkpoint inhibitor therapy for oculoplastic applications, specifically eyelid and conjunctival melanomas.10 However, there is limited clinical experience with the use of these drugs for this indication. Eyelid and conjunctival melanomas were not specifically studied in the trials leading to the development of these therapies, resulting in limited knowledge of their potential benefits and risks. This chapter reviews the available literature regarding checkpoint inhibitors for eyelid and conjunctival melanomas.