A Case of Pernicious Anemia Induced by Atezolizumab in Hepatocellular Carcinoma and Renal Cell Carcinoma

BACKGROUND Anemia derived from immune checkpoint inhibitor (ICI) is recognized as a systemic immune-related adverse event (irAE). However, only a few studies reported regarding pernicious anima (PA) or megaloblastic anemia induced by vitamin B12 (Vit.B12) deficiency after ICI treatment. Vit.B12 deficiency-induced PA remains unclear as an irAE. CASE REPORT We present a case of a 68-year-old man with hepatocellular carcinoma and renal cell carcinoma who developed Vit.B12 deficient megaloblastic anemia after the induction of atezolizumab-containing chemotherapy. Laboratory findings revealed hemoglobin of 6.1 g/dL with signs of hemolysis, gastric parietal cell antibody positivity, and gastrin level elevations. He tested negative for Helicobacter pylori antibodies. Upper gastrointestinal endoscopy showed atrophic mucosa that affected almost the entire stomach. The loss of gastric folds and marked vascular visibility were observed. We defined it as open type (O-3) atrophic gastritis, although histopathological examination was not performed. Based on these findings, the anemia was considered megaloblastic anemia induced by Vit.B12 deficiency (PA). The anemia demonstrated partial recovery (hemoglobin of 9.5 g/dL) with the resolution of hemolytic pattern after mecobalamin administration. We found that PA was associated with parietal cell antibody production triggered by atezolizumab, in which the removal of immune checkpoint brakes by atezolizumab may reveal this pathogenesis. Because PA is recognized as the progressive status of autoimmune gastritis, ICI treatment-induced PA is suggested to emerge at the late phase. CONCLUSIONS PA is indicated as a potential complication of ICI-containing chemotherapy. Measuring Vit.B12 levels is essential when encountering cases of anemia and gastritis during ICI treatment.