Immune checkpoint inhibitors induced autoimmune hemolytic anemia in patients with malignant cancer.

Abstract

Background: Autoimmune hemolytic anemia (AIHA) is a rare but potentially life-threatening hematologic immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs). This study reports 3 new cases of ICI-induced AIHA from three medical centers in China and places them in the context of existing literature.

Methods: Three patients with AIHA following ICI therapy were identified from The Second Xiangya Hospital, Qilu Hospital, and Nanping First Hospital. A PubMed search up to June 1, 2026, was conducted to collect previously reported cases with sufficient clinical details.

Results: A total of 51 cases were analyzed, including three new patients and 48 from published reports. The mean age was 65.2 years, and 47.1% were male. The most common tumor types were melanoma (49.0%) and non-small cell lung cancer (27.5%). Most cases were associated with anti-PD-1 agents, particularly pembrolizumab and nivolumab, and AIHA typically developed early during ICI therapy. Corticosteroids were the primary treatment, with 92.2% achieving hematologic recovery or improvement. Four deaths (7.8%) were attributed to severe hemolysis. All three newly identified patients had pre-existing anemia before ICI initiation.

Conclusions: ICI-induced AIHA usually occurs early during ICI therapy and responds favorably to corticosteroid-based treatment. Pre-existing anemia in our cases should be regarded as a hypothesis-generating observation rather than evidence of a specific risk factor, underscoring the need for early hemolysis work-up and close monitoring when anemia worsens after ICI exposure.