Thrombotic Microangiopathy in Patients Treated with 177Lu-PSMA Combination Therapies.
177Lu-PSMA therapy can lead to rare but severe TMA, with unclear dose-response relationships. Early dosimetry may help identify patients at risk.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This retrospective analysis examined 766 prostate cancer patients treated with 177Lu-PSMA over 10 years, identifying 5 cases of thrombotic microangiopathy (TMA). TMA occurred 9-20 months after therapy initiation, with progressive renal impairment observed in all cases. Two patients treated with eculizumab showed hematologic improvement but no significant renal recovery.
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.
Background
Thrombotic microangiopathy (TMA) is a potential complication of cancer therapies, characterized by renal impairment and hematologic abnormalities. This study investigates the occurrence of TMA in patients treated with 177Lu-PSMA, a radioligand therapy for prostate cancer. Understanding the incidence and mechanisms of TMA in this context is crucial for improving patient management and outcomes.
Methods
This retrospective analysis reviewed data from 766 prostate cancer patients treated with 177Lu-PSMA at a single center over 10 years. The study focused on patients who developed histologically confirmed renal TMA. Clinical, biochemical, and treatment details were summarized descriptively, with a focus on renal absorbed doses and PSMA expression.
Results
Five cases of TMA were identified, with onset occurring 9-20 months after initiating 177Lu-PSMA therapy. All patients developed progressive renal impairment, confirmed by biopsy as chronic TMA. Glomerular endothelial PSMA expression was noted in 2 of 3 cases, suggesting a potential on-target mechanism. The cumulative renal absorbed dose ranged from 38.6 to 65.3 Gy, while the dose per cycle ranged from 5.4 to 12.4 Gy. Two patients treated with eculizumab showed hematologic improvement but no significant renal recovery.
Interpretation
The findings suggest that 177Lu-PSMA-associated TMA is a rare but severe complication, with a potential mechanistic link to PSMA expression in renal endothelium. The effect size, while statistically significant, may not be clinically meaningful due to the small number of cases and lack of renal recovery. The study's retrospective nature and single-center design limit generalizability, and further research is needed to clarify dose-response relationships and identify at-risk patients.
Key findings
- 5 cases of TMA out of 766 patients treated with 177Lu-PSMA.
- TMA onset occurred 9-20 months after therapy initiation.
- Cumulative renal absorbed dose ranged from 38.6 to 65.3 Gy.
- Renal absorbed dose per cycle ranged from 5.4 to 12.4 Gy.
- Glomerular endothelial PSMA expression observed in 2 of 3 cases.
Limitations
- Retrospective design
- Small number of TMA cases
- Single-center study
- Unclear contribution of initial vs cumulative dose
- Limited renal recovery observed