Hematological immune-related adverse events associated with checkpoint inhibitors

The use of immune checkpoint inhibitors (ICIs) has expanded substantially across tumor types, establishing them as a cornerstone of modern oncology. However, the frequency and severity of immune-related adverse events (irAEs) remain underestimated, particularly hematologic toxicities, which can be life-threatening and require distinct management approaches compared to cytotoxic or targeted therapies.

We performed literature reviews using PubMed to identify and analyze reported cases of the most frequent hematologic irAEs; autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and pure red cell aplasia (PRCA), in patients with solid tumors. In parallel, we report three illustrative cases from our institution to highlight diagnostic pitfalls and management strategies.

The median onset of hematologic irAEs occurs after approximately 3 cycles of ICI therapy for AIHA and ITP, and after 4 cycles for PRCA. Most patients achieved remission with corticosteroid therapy; however, 10-15% were steroid-refractory or relapsed, requiring second-line immunosuppressive agents. Rechallenge with ICIs remains controversial due to a recurrence rate of irAE, although it may be feasible and clinically beneficial in carefully selected patients.

As the use of ICIs continues to rise, prompt recognition and management of hematologic irAEs are critical to minimize morbidity and to avoid premature discontinuation of immunotherapy. Increased clinician awareness and standardized diagnostic algorithms are essential to preserve both safety and efficacy.