Bispecific Dual-Immune Checkpoint Inhibitor Associated Cutaneous Toxicity: A Report of Lorigerlimab Adverse Skin Reaction in Two Cancer Patients.

Lorigerlimab is a dual bispecific antibody (BsAb) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 that is used for treatment of advanced solid cancers such as metastatic castration-resistant prostate carcinoma. Reported cutaneous immune-related adverse events (irAEs) of lorigerlimab, such as pruritus and rash, are mostly manageable. However, to the best of our knowledge, the clinical histopathologic features of irAEs of the skin to dual immune checkpoint blockade with BsAbs have not been characterized. We report herein on lorigerlimab-associated lichenoid and vacuolar interface dermatitis in two patients with metastatic castration-resistant prostate adenocarcinoma. Case 1 had a violaceous, papular eruption and a lichenoid, perivascular histopathologic reaction pattern that responded well to temporary withholding of lorigerlimab and to corticosteroids. Case 2 presented with a more severe rash characterized by mixed clinical features of psoriasiform, eczematous, and morbilliform eruption and a histopathologic pattern of vacuolar interface changes with superficial perivascular lymphocytic infiltrate, scattered dyskeratotic keratinocytes, and focal acantholysis. The eruption was refractory to treatment, despite the patient withholding lorigerlimab, leading to complete discontinuation of lorigerlimab. This report highlights the importance of histopathologic evaluation in guiding treatment decisions for lorigerlimab-associated irAEs and underscores the need for further research into its dermatologic irAEs.