Carfilzomib-Associated Thrombotic Microangiopathy in a Multiple Myeloma Patient: Complement Genetic Alterations Impact and Eculizumab Therapy.

Carfilzomib is a second-generation proteasome inhibitor used in relapsed or refractory multiple myeloma (MM). Although effective, it can be associated with rare but life-threatening complications. We describe a 73-year-old woman with relapsed IgG-kappa MM who developed thrombotic microangiopathy (TMA) and acute kidney injury (AKI) requiring hemodialysis, three weeks after initiating a carfilzomib-based regimen. Genetic testing showed a homozygous CFHR3-CFHR1 deletion and variants of uncertain significance in the CFI and ADAMTS13 genes. The patient underwent plasmapheresis followed by treatment with eculizumab, resulting in full renal recovery. This case highlights a rare but potentially reversible complication of carfilzomib therapy, likely driven by complement activation and endothelial injury. It also underscores the role of genetic predisposition and the therapeutic benefit of complement inhibition with eculizumab. Early recognition, drug discontinuation, and consideration of both genetic screening and complement inhibition may improve outcomes in at-risk patients.