Locally Advanced Conjunctival Squamous Cell Carcinoma not Responsive to Immune Checkpoint Inhibitor Therapy: 3 Cases and a Literature Review

Three patients with locally advanced conjunctival squamous cell carcinoma originating in the inferior fornix were treated with immunotherapy: a 74-year-old male was treated with 4 cycles of cemiplimab, a 54-year-old female was treated with 3 cycles of pembrolizumab, and a 69-year-old female was treated with 2 cycles of pembrolizumab. Tumor progressed in all 3 patients on immunotherapy, requiring orbital exenteration for disease control. Tumor mutational burden was low in all 3 patients: 1.2, 8.1, and 7.1 mut/Mb. Review of the literature reveals 18 cases of invasive conjunctival squamous cell carcinoma treated with immunotherapy in addition to the 3 cases reported herein, with tumors of responders tending to have a higher tumor mutational burden than those of nonresponders. There is increasing evidence that conjunctival squamous cell carcinoma originating in the sun-protected inferior fornix/inferior palpebral conjunctiva has low tumor mutational burden and is less likely to respond to immunotherapy than squamous cell carcinoma of bulbar conjunctival origin.