32963 Nivolumab-induced vasculopathy: A novel immunotherapy reaction

Abstract

Immune checkpoint inhibitor therapy has revolutionized treatment of metastatic melanoma. However, both novel and fatal adverse events continue to be reported. We present a case of a 45-year-old Caucasian woman who developed severe small-vessel vasculopathy on nivolumab therapy for metastatic melanoma. Eight years prior to presentation, she had a resection of a stage IA melanoma. Four months prior to presentation, she developed an axillary mass prompting CT and PET imaging with subsequent axillary node biopsy. Biopsy findings showed poorly differentiated tumor consistent with her primary melanoma and nivolumab therapy was initiated. After her 4th cycle, she presented to the ED with dusky, indurated plaques on her breasts, lower abdomen, proximal legs, and buttocks covering <30% TBSA. Initial punch biopsies showed suppurative dermatitis with hemorrhage and Gram-positive cocci. Eleven days later, these areas evolved into ulcerations with eschars. Repeat incisional biopsies showed extensive epidermal and dermal necrosis with small vessel thrombotic vasculopathy. Laboratory values including factor V Leiden, antiphospholipid antibodies, c-ANCA/p-ANCA, PT/PTT/INR, protein C & S deficiency, cryoglobulins, negative blood cultures, among other tests, excluded hypercoagulable and infectious etiologies. Given the timing of lesions and exclusion of other causes, nivolumab therapy was determined the cause of her vasculopathy and was subsequently held. Apixaban was initiated, resulting in the cessation of new lesions. This case illustrates a vasculopathy mediated by a novel mechanism secondary to immunotherapy. We believe it is essential clinicians are aware of this novel reaction and its management as late recognition could prove fatal for patients.