Sequential Use of Prednisolone and Cyclosporine Is Effective in the Management of Immunotherapy-Related Hemolytic Anemia

Abstract

Immune checkpoint inhibitors (CPIs) can cause immune-related organ dysfunctions, including nephritis, pneumonitis, thyroiditis, hepatitis, colitis and more rarely hematological toxicities like immune-related autoimmune hemolytic anemia (irAIHA). Very few cases of irAIHA associated with immunotherapy have been reported, and treatment protocols remain unclear. This is partly because not all irAIHA cases are Coomb’s test positive. Causes of anemia in cancer patients undergoing treatment with chemotherapy with or without immunotherapeutic agents can also be multiple. This makes it difficult to initially diagnose irAIHA, especially when CPIs are used concurrently with chemotherapy. Once alternate causes have been ruled out, a treatment plan for irAIHA is initiated based on grade of the anemia. Grade 1-2 irAIHA cases are managed with supportive interventions. However, cessation of therapy is recommended for life-threatening (grade 4) toxicity, severe (grade 3) toxicity that is recurring, or moderate (grade 2) toxicity that does not resolve with appropriate treatment for 3 months. Management of irAIHA usually involves methylprednisolone for 2 - 4 weeks with a slow taper after hemoglobin has normalized. But many cases do not respond to steroids alone and require cessation of immunotherapy or selecting alternate immunosuppressive agents. We report a protocol for treatment of grade 4 irAIHA secondary to programmed death protein 1 (PD-1) blocker pembrolizumab.