Thrombotic Microangiopathy (Tma) After Treatment With Nivolumab In Advanced Gastric Cancer

Immune checkpoint inhibitors have opened up new avenues for cancer treatment. However, immune-related adverse events (irAEs) remain a concern. Thrombotic microangiopathy (TMA) is a rare irAE that is associated with a high mortality rate in cancer therapy. A 63-year-old man was admitted to our hospital because of disturbed consciousness, anemia, and thrombocytopenia. Three years prior he had been diagnosed with gastric cancer; a total gastrectomy revealed incurable peritoneal metastasis. S-1 plus oxaliplatin as first-line chemotherapy was initiated, followed by nab-paclitaxel as second-line and nivolumab as third-line. On the 11th day of a third course of nivolumab, the patient was transported to hospital but became comatose after admission. A transfusion did not improve his anemia. Bleeding after systemic CT was not found. His peripheral blood test revealed hemolysis, elevated indirect bilirubin, decreased haptoglobin, and apparently crushed red blood cells. However, negative direct and indirect Coombs tests ruled out autoimmune hemolytic anemia. A negative coagulation test discounted disseminated intravascular coagulation (DIC). Hemolytic uremic syndrome (HUS) was also excluded in the absence of a history of enteric infection. Therefore, we suspected thrombotic thrombocytopenic purpura (TTP). Plasma exchange (PE) was quickly initiated but the patient's condition worsened. He died on the third hospital day. Post-death, A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity showed no decrease, leading us to diagnose the cause of death as TMA. To date, few reports exist of TMA as an irAE. However, distinguishing between TTP, HUS, DIC, and TMA is difficult. In addition, patients require immediate treatment since the mortality rate of TTP is more than 90% without emergency PE, which was, unfortunately, ineffective in our case. We report a rare case of TMA as an irAE during treatment with nivolumab for advanced gastric cancer.