Hematologic immune-related adverse effects of immune checkpoint inhibitors: a review

Immune checkpoint inhibitors (ICIs) targeting CTLA-4, PD-1, and PD-L1 have transformed cancer therapy but may trigger rare, sometimes fatal hematologic immune-related adverse events (irAEs). The most frequent hematologic irAEs are anemia, thrombocytopenia, and pancytopenia, which occur more often with CTLA-4 inhibitors and in patients receiving combination therapy. Risk is heightened when ICIs are combined with chemotherapy or radiation. Common symptoms include fatigue, abnormal bleeding, easy bruising, and recurrent infections. Diagnosis relies on laboratory studies, histologic evaluation, and review of medication history. Management typically involves ICI discontinuation and immunosuppression with corticosteroids or rituximab; adjunctive options include IVIG, transfusions, or plasmapheresis depending on severity. Research is also exploring cytokines such as IL-2, IL-7, and IL-15 for ICI-related lymphopenia. Current evidence is drawn mainly from case reports and small series, highlighting the need for larger studies to clarify incidence, mechanisms, and optimal management. Recent pharmacovigilance and outcomes data confirm these events remain rare and can present late, underscoring the need for long-term surveillance and robust monitoring systems [Fletcher K and Johnson DB 2024; Durbin SM et al. 2025; Yang Y. et al. 2024; Han X. et al. 2025].