Management and Outcomes of Hematological Immune-related Adverse Events: Systematic Review and Meta-analysis

Data regarding clinical outcomes and management of hematological manifestations of immune checkpoint inhibition (ICI) is limited to case reports, series, and a few retrospective reviews. We aimed to determine the rate of response of hematological immune-related adverse events (irAEs) to immunosuppressive therapy. MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to the present day. Retrospective reports were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. The primary outcome of this study was the rate of response to immunosuppression. Eighty studies (14 case series and 66 individual case reports) were analyzed with a total of 135 patients with ICI-related hematological irAEs. Data analysis showed an average proportional response rate to immunosuppression among hematological irAE entities of 50% (range: 25%-70%). The heterogeneity index (I (2)) was 0% among reports within each entity. There is a wide spectrum of hematological manifestations to ICI therapy, and to date there is no large randomized-controlled trial data to evaluate the efficacy of treatment strategies for hematological irAEs. We found a variable overall response rate to immunosuppression therapy of around 50%, without statistically significant heterogeneity among different irAE types but significant differences among the different countries of publication. Future studies evaluating the optimal dose and duration of immunosuppressive agents for patients with hematological irAEs should be undertaken.