Acquired thrombotic thrombocytopenic purpura associated with immune checkpoint inhibitors: A real-world study of the FDA adverse event reporting system.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a risk of developing immune-related adverse events, most commonly colitis, dermatitis, hepatitis, and thyroiditis. Rare autoimmune hematologic toxicities have been reported but are less well-described in the literature. Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening autoimmune condition that has been reported with ICIs but has been limited to case reports.

METHODS: We performed a retrospective observational analysis of the United States Food and Drug Administration Adverse Event Reporting System (FAERS) data. We searched for cases of TTP reported with exposure to ICIs from initial FDA approval for each agent to December 31, 2021. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR).

RESULTS: There were 35 reports of TTP with ICIs in the FAERS database, including atezolizumab (n = 7), durvalumab (n = 2), nivolumab (n = 18), and pembrolizumab (n = 8). The ROR was significant for atezolizumab (ROR 6.22, 95% CI 2.96-13.09), nivolumab (ROR 3.16, 95% CI 1.99-5.03), and pembrolizumab (ROR 2.56, 95% CI 1.28-5.12).

CONCLUSIONS: There is a significant reporting signal of TTP with several ICI agents. Clinicians should be aware of and monitor for signs of this potentially serious adverse event.