Eculizumab use in drug-induced thrombotic microangiopathy with CFHR1–CFHR3 deletion

Abstract

Drug-induced thrombotic microangiopathy (DI-TMA) is a rare but severe complication of chemotherapeutic agents such as gemcitabine and bevacizumab. Although discontinuation of the offending agent and supportive care are standard, response may be inadequate in cases involving complement dysregulation. Eculizumab, a terminal complement inhibitor, has been utilized in complement-mediated TMA and select DI-TMA cases. We report a case of biopsy-confirmed TMA following gemcitabine and bevacizumab therapy in a patient with high-grade serous ovarian carcinoma. Genetic testing revealed homozygous deletion of CFHR1 and CFHR3, supporting a complement-mediated mechanism. The patient received eculizumab with partial hematologic response but no renal recovery. This case highlights the potential utility of genetic testing to predict eculizumab responsiveness in DI-TMA and to support targeted complement inhibition where standard therapy fails.