Immune checkpoint inhibitor-related thrombocytopenia: Incidence, risk factors, and effect on overall survival.
Authors: Haddad Tyler , Zhao Songzhu , Li Mingjia , Patel Sandip H. , Johns Andrew , Grogan Madison , Lopez Gabrielle , Miah Abdul , Wei Lai , Tinoco Gabriel , Riesenberg Brian P , Li Zihai , Bertino Erin Marie , Kendra Kari Lynn , Otterson Gregory Alan , Presley Carolyn J , Owen Dwight Hall 
Published: June 2021

e14549

Background: Immune checkpoint inhibitors (ICI) are a standard of care therapy for patients with many different cancers. ICI are generally well tolerated but are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity and risk factors for irTCP are unknown. Although other irAE have been associated with clinical benefit, little data is available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI. Methods: We conducted a retrospective review of sequential patients with any solid or hematologic cancer treated with ICI between 2011 and 2017 at The Ohio State University Comprehensive Cancer Center. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. Thrombocytopenia grading was performed utilizing the Common Terminology Criteria for Adverse Events version 5.0. Attribution to ICI was defined as timing after ICI initiation, lack of alternative causes, and improvement with either holding treatment or use of immune suppressive therapy. Overall survival (OS) was calculated from the date of initiation of ICI to death from any cause or date of the last follow-up examination. Cox proportional hazard models were used to examine the associations between platelet categories with OS. Median OS was estimated using Kaplan-Meier method with 95% CI. Results: We identified 1,038 patients treated with ICI therapy after excluding patients with baseline thrombocytopenia. The median age was 61.4; 613 (59.1%) were male and 613 (59.1%) had history of smoking. The most common cancer types were melanoma (n = 337, 32.5%), lung (n = 213, 20.5%), and renal cell carcinoma (n = 114, 11%). The most common ICI were PD1/L1 (n = 729, 70.2%) and CTLA4 (n = 191, 18.4%). Overall, 89 (8.6%) patients developed grade ≥3 thrombocytopenia; twenty were attributed to ICI (1.93% overall). Patients who developed ≥3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (5.45 vs 11.3 months; HR. 2.077, 95% CI 1.231, 3.503; log-rank p = 0.005). Patients with ≥3 irTCP also had shorter survival compared to those without thrombocytopenia of any etiology (5.45 vs 13.3 months; HR 2.247, 95% CI: 1.414, 3.571; p < 0.001). irTCP was more common among those treated with PD1/L1 (p = 0.03) but was not associated with cancer type, smoking status, age, gender, race, or line of therapy. Conclusions: Type of immunotherapy is related to irTCP, whereas cancer type and line of therapy are not. Unlike other irAEs, we found that irTCP was associated with shorter overall survival. These findings provide important insight into a poorly understood and rare toxicity. irTCP should be evaluated in more extensive studies to better inform clinical decision making.