Carfilzomib-Induced Thrombotic Microangiopathy: Rapid Renal Recovery with Eculizumab Therapy

Introduction: Drug-induced thrombotic microangiopathy (DI-TMA) is a rare, life-threatening condition caused by immune-mediated or toxic mechanisms, leading to multisystem organ damage, most commonly affecting the kidneys. Carfilzomib, a proteasome inhibitor approved for relapsed/refractory multiple myeloma (MM), has been associated with TMA, often causing severe kidney injury. Complement dysregulation has emerged as a key factor in DI-TMA pathogenesis, and therapies like eculizumab have shown promising outcomes. We present a case of carfilzomib-induced TMA complicated by dialysis-dependent end stage kidney disease (ESKD), successfully treated with eculizumab. Case Description: A 73-year-old woman with a history of colon carcinoma and refractory IgG-kappa MM presented after 22 cycles of carfilzomib with fever, hypertension, oliguria and peripheral edema. She appeared pale, febrile (39.7°C), hypertensive (177/75 mmHg), and hypervolemic. Labs showed anemia (7.6 g/dL), thrombocytopenia (11,000/µL), elevated LDH (1549 U/L), over 1% schistocytes in the peripheral smears, and undetectable haptoglobin (< 5.8 mg/dl). Complement C3 was mildly reduced (85 mg/dL); ADAMTS13 activity was normal (59%). Renal function revealed creatinine of 6.2 mg/dL (baseline 0.9), urea 197 mg/dL, hyperkalemia, and metabolic acidosis. Renal ultrasound was unremarkable. Carfilzomib-induced TMA was diagnosed; dialysis was started for persistent uremia and oliguria. Eculizumab was initiated five days later (900 mg weekly). A biopsy at two weeks confirmed TMA without of evidence monoclonal-related kidney disease. Eculizumab was continued at 1200 mg biweekly and by week four, hematologic parameters normalized and schistocytes resolved. Dialysis was discontinued by week eight. At three months, serum creatinine stabilized at 1.3 mg/dL, and eculizumab was discontinued. Discussion: Carfilzomib-induced TMA is a rare but serious complication. Its diagnosis is often delayed due to non-specific or renal-limited presentation and the lack of standardized criteria. While biopsy confirms the diagnosis, cytopenias usually preclude it. Evidence supports that early complement blockade with eculizumab leads to hematologic and renal recovery. Although optimal dosing remains unclear, this case illustrates that even dialysis-dependent ESKD can be reversed with timely therapy.