Cross-organ examination of hematologic toxicities from immune checkpoint inhibitors: insights from real-world data

Immune checkpoint inhibitors (ICPis) are widely used clinically to improve the prognosis of various cancers. However, little is known about their hematologic immune-related adverse events (irAEs). This study aimed to comprehensively investigate the incidence and clinical characteristics of irAEs induced by ICPis through a cross-organ research approach.

Patients who received at least one ICPi dose at the Osaka International Cancer Institute between January 2014 and September 2021 were reviewed, irrespective of their tumor type. We analyzed the cumulative incidence of hematological irAEs and investigated the clinical course of patients who underwent bone marrow examination owing to suspected hematological irAEs.

During the study period, 1500 patients in total received ICPis. Based on clinical data and the histopathological evaluation of bone marrow samples, we identified seven cases of hematologic irAEs (four of immune thrombocytopenia, two of hemophagocytic lymphohistiocytosis, and one of agranulocytosis). Additionally, we observed six cases of primary hematologic disease, four of bone marrow findings consistent with cytopenia and subsequent recovery secondary to infections or cytotoxic agents, two of bone marrow involvement by primary cancer, and one of an unknown cause. With the median follow-up of 297 days (0-2087 days), the cumulative incidence rates of hematologic irAEs at 90 days and 1 year were 0.1% (95% CI, 0.0-0.4) and 0.4% (95% CI, 0.2-1.0), respectively. None of the patients with hematological irAEs died.

Severe hematological irAEs are rare but can be life-threatening. When hematological abnormalities are detected during ICPi therapy, it is important to explore the possibility of irAEs, including bone marrow abnormalities.