Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review

Background: Immune checkpoint inhibitors (CPI) are widely used in modern oncology and have improved the prognosis of lung cancer, malignant melanoma, and other malignancies. Unlike cytotoxic chemotherapy, drugs such as nivolumab, pembrolizumab, and ipilimumab are associated with immune-related adverse effects. We recently observed a patient with lung cancer who developed a fulminant warm antibody autoimmune hemolytic anemia (AIHA). Objectives: Investigate the frequency and prognosis of AIHA secondary to CPI in a public database and review the literature. Results: A total of 68 cases were identified in the database of the Food and Drug Administration (FDA), 43 were associated with nivolumab, 13 with pembrolizumab, seven with ipilimumab, and five with atezolizumab. All episodes of AIHA were listed as serious. If the total number of adverse events cases reported to the FDA is taken as a reference, AIHA is rare, but occurred more frequently with PD-1 or PD-L1 targeting agents (0.15%-0.25%) than with CTLA-4 inhibitors (0.06%). In addition to our case, the literature review identified 11 similar cases. Most cases of AIHA responded to steroids, but two of 12 were fatal. Conclusion: We describe AIHA as a new and serious immune-related side effect of CPI. Early aggressive management is necessary.