Immune Checkpoint Inhibitors Induced Autoimmune Haemolytic Anemia: Case Series and Literature Review

Abstract Immune checkpoint inhibitors (ICIs) have brought a revolution to the anti-cancer treatment, however, they also triger a unique spectrum of immune-related adverse events (irAEs). Among irAEs, haemopoietic AEs are rarely reported and mostly severe or even life-threatening, especially autoimmune haemolytic anemia (AIHA). AIHA is presumed to relate to the abnormal formation of circulating autoantibodies against red cell membrane antigens. It usually cannot be discovered timely because of atypical symptoms. It is diagnosed according to presence of hemolysis evidences such as decrease of haemoglobin, increase of indirect bilirubin and lactate dehydrogenase (LDH), urobilinogen, and positive direct antiglobulin test (DAT). Treatments of AIHA are according to clinical experience and consensus, which have not been verified by prospective trial. Here we investigate previous reported ICIs induced AIHA cases including thirty detailedly documented patients. On the other hand, we report three patients who developed AIHA after three different anti-PD-1 antibodies. Most of them were aged patients with melanoma or NSCLC, developed AIHA by anti-PD-1 antibodies and relived with glucocorticoid. 43.3% of previous cases and all of our observed cases had anemia before ICIs treatment, which reminds us of anemia as a risk factor for ICIs induced AIHA. By screening parameters like complete blood examination, reticulocyte, liver function test or DAT test prior to immunotherapy, doctors could exclude pretreatment haemolytic anemia or be aware of post ICIs AIHA. Thus, it is possible to avoid the potentially life-threatening AIHA, or improve the level of pre-alarm and treatment ability of AIHA.