Abstract
INTRODUCTION: Immune-related adverse events (irAEs) are a group of autoimmune syndromes that arise following therapy with immune checkpoint inhibitors (ICIs) and are characterized by disinhibition of cell-mediated immunity and decreased self-tolerance. First line treatment of irAEs is typically steroids. Severe irAEs that are refractory to steroids can be life threatening and treatment protocols are an area of unmet need. Standardized clinical guidelines for management of severe corticosteroid refractory irAEs are currently not available and thus are an area of unmet need. CASES: We present two patients who were treated with nivolumab and subsequently developed steroid refractory irAEs in the forms of transverse myelitis, arthritis, and peri-engraftment respiratory distress syndrome. CONCLUSIONS: Treatment with a single high dose of cyclophosphamide resulted in rapid and sustained clinical improvements in two patients experiencing steroid refractory irAEs following ICI therapy. Cyclophosphamide may benefit patients with wide spectrum of irAEs while having a favorable toxicity profile.