Incidence, Clinical Characteristics, Management, and Outcomes of Hematologic Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors: A Single-Center Japanese Retrospective Cohort Study.

Abstract

Introduction: Immune-related adverse events (irAEs) are complications associated with immune checkpoint inhibitors (ICIs). Hematologic irAEs (heme-irAEs) are rare but potentially serious and may interfere with cancer treatment. However, their clinical characteristics remain insufficiently described.

Methods: We conducted a single-center retrospective study using the National Cancer Center Hospital East medical database from April 1, 2014, to March 31, 2024. Potential heme-irAE cases were identified using diagnostic name searches, bone marrow examination records, and positive DAT results and were followed by chart review to exclude alternative etiologies, such as chemotherapy-related myelosuppression, marrow involvement, infection, and hematologic malignancy.

Results: Of the 3371 patients treated with ICI-containing regimens, 40 patients developed heme-irAEs, indicating an observed incidence of 1.2%. The most common heme-irAE reported was immune thrombocytopenia, and 85.0% of these events were Grade 3 or higher. The median time from ICI initiation to heme-irAE onset was 12 weeks. For all affected patients included in the regimen-specific onset-time comparison, the median time to heme-irAE onset appeared shorter with dual ICI therapy without chemotherapy than with ICI monotherapy, although this descriptive comparison was based on a small number of cases. ICI-containing regimens were interrupted or discontinued in most patients, and systemic corticosteroids were administered to 25 patients, 18 of whom achieved hematologic improvement. Cancer treatment was resumed or continued for 20 patients, with no recurrent heme-irAEs observed during the follow-up period. In an exploratory landmark analysis, hematologic response was associated with longer survival after heme-irAE onset.

Conclusion: Heme-irAEs were rare but frequently severe in this Japanese single-center cohort. Their occurrence was associated with prolonged interruption of cancer treatment, underscoring the importance of early recognition, careful diagnostic evaluation, and multidisciplinary management of heme-irAEs. Our findings regarding dual ICI therapy, survival, and subsequent ICI therapy after heme-irAE onset should be interpreted as exploratory.