Immune thrombocytopenia in patients treated with immune checkpoint inhibitors Available to Purchase

• Immune checkpoint inhibitor-associated ITP (ICI-ITP) has an incidence of 1 in 400, with 30% developing recurrence with ICI rechallenge.

• Although most patients (75%) recover, ICI-ITP and its severity are independently and monotonically associated with a higher risk of death.

Immune checkpoint inhibitor-associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016-2023 at 29 U.S. hospitals across seven major cancer centers to identify cases of ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86,467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage 4 cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (IQR, 4-18) after ICI initiation, with a median nadir platelet count of 41 x109/L (IQR, 17-64). Patients were treated with glucocorticoids (n=106, [49.5%]), immune globulin (n=39 [18.2%]), and thrombopoietin receptor agonists (n=29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP compared with those without ICI-ITP (adjusted HR 2.96 [95% CI, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.