Thrombotic Microangiopathy in Patients Treated with <sup>177</sup>Lu-PSMA Combination Therapies.

Abstract

Over a period of 10 y, our center treated 766 patients with prostate cancer using 177Lu-PSMA (177Lu-PSMA-617 or 177Lu-PSMA I&T). We report 5 cases of 177Lu-PSMA-induced thrombotic microangiopathy (TMA). Methods: In this retrospective analysis, we reviewed data from all patients at our center who developed histologically confirmed renal TMA after 177Lu-PSMA. Clinical, biochemical, and treatment details were summarized descriptively. Results: TMA occurred 9-20 mo after initiating 177Lu-PSMA therapy. Four patients had a normal baseline estimated glomerular filtration rate (>90 mL/min/1.73 m2). All patients developed progressive renal impairment with biopsy-proven chronic TMA. Glomerular endothelial PSMA expression was observed in 2 of 3 cases, suggesting a potential on-target mechanism of injury via an increased cumulative organ dose of 177Lu-PSMA. The cumulative renal absorbed dose ranged from 38.6 to 65.3 Gy, and the renal absorbed dose per cycle ranged from 5.4 to 12.4 Gy. Two patients received complement inhibition with eculizumab, which improved hematologic features without meaningful renal recovery. Conclusion: 177Lu-PSMA-associated TMA is a rare but a potentially severe complication of treatment. The contribution of initial versus cumulative renal absorbed dose remains unclear, and early dosimetry may help identify at-risk patients.