Autoimmune Hematological Toxicities of Immune Checkpoint Inhibitors: A Real-World Pharmacovigilance Database Analysis

BACKGROUND:

Autoimmune hematological toxicities are rarely reported from the use of checkpoint inhibitors. However, there have been several cases of autoimmune hemolytic anemia, immune thrombocytopenia, hemophagocytic lymphohistiocytosis (HLH), and immune mediated cytopenias that have been reported in patients who were treated with checkpoint inhibitors. We performed a retrospective analysis of data of adverse effects of drugs that has been made available to public by the FDA.

METHODS:

The FDA has made data on adverse effects of various treatments available to the public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the autoimmune hematological toxicities of various checkpoint inhibitor therapies available at FAERS for the years 2020-2022.

RESULTS:

We reviewed the reported side effects of PD-1 inhibitors (pembrolizumab, nivolumab, cemiplimab, dostarlimab), PDL-1 inhibitors (atezolizumab, avelumab, durvalumab), and CTLA-4 inhibitors (ipilimumab) from FAERS. A total of 5,195 hematological toxicities from immunotherapies were reported from 2020-2022. Out of those, 483 (9.3%) were autoimmune hematological toxicities. The most common autoimmune complications were autoimmune hemolytic anemia (21.9%), immune thrombocytopenia (36%), autoimmune neutropenia (4.1%), HLH (36.2%) and thrombotic/idiopathic thrombocytopenic purpura (ITP/TTP) (1.8%). Nivolumab had the highest incidence of autoimmune hematological events out of all immune checkpoint inhibitors. Since cemiplimab and dostaralimab are relatively newly being utilized for treatment, there has not been much reported data.

CONCLUSIONS:

Out of the reported cases of hematological adverse reaction to check point inhibitor, 9.3% were autoimmune toxicities. There was no statistical difference in rate of autoimmune toxicities caused by PD1, PDL1 or CTLA 4 inhibitors. As utilization of newer immune checkpoint inhibitors increase, we would need to re-evaluate incidence of autoimmune hematological adverse reactions.

Master:Cardinal Health: Membership on an entity's Board of Directors or advisory committees; Aptitude health: Membership on an entity's Board of Directors or advisory committees; curio sciences: Membership on an entity's Board of Directors or advisory committees; Blue Bird Bio: Current holder of stock options in a privately-held company; Toxicity: Current holder of stock options in a privately-held company; Gilead: Current holder of stock options in a privately-held company; Jasper: Current holder of stock options in a privately-held company.