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Kidney Week

Abstract: PO2199

CKD After 225Ac-PSMA617 Therapy in Patients with Advanced Metastatic Prostate Cancer: A Report of Two Cases

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Report

  • 1500 Onco-Nephrology

Authors

  • Pelletier, Karyne, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Côté, Gabrielle, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Kitchlu, Abhijat, University Health Network, University of Toronto, Toronto, Ontario, Canada
Introduction

A promising therapeutic efficacy has been demonstrated with targeted radionuclide therapy (TRNT) using 225Ac-PSMA617 in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). However, these novel agents may be associated with significant toxicity. As seen in animal models, the multiple alpha particles generated in the decay chain of 225Ac may accumulate in the renal tubular cells, resulting in nephropathy. We report our experience with 225Ac-PSMA617 therapy in 2 patients with advanced mCRPC who developed kidney injury.

Case Description

Patient 1 is a 68-year-old man with widely metastatic mCRPC despite multiple lines of therapy and secondary chronic hydronephrosis with bilateral nephrostomy tubes. He received 3 rounds of 225Ac-PSMA617 in 2-month intervals. Baseline serum creatinine was 1.6 mg/dL (eGFR 44 mL/min/1.73m2) and it increased up to 3.3 mg/dL (eGFR 18 mL/min/1.73m2) after 225Ac-PSMA617 therapy. A kidney biopsy was obtained and revealed severe interstitial fibrosis with ongoing tubular injury and interstitial inflammation. A trial of corticosteroids therapy was attempted with no improvement in kidney function. 225Ac-PSMA617 therapy was discontinued because of related kidney failure.

Patient 2 is a 67-year-old man with mCRPC with progression on multiple prior therapies. He first initiated Lu177-PSMA and one year later this was combined with 225Ac-PSMA617 in 2-month intervals. He received 5 rounds of 225Ac-PSMA617 in total, the last round being complicated with grade 3 cytopenias leading to cessation of treatment. Baseline serum creatinine at initiation of TRNT was 1.0 mg/dL (eGFR 82 mL/min/1.73m2). He subsequently developed progressive CKD and serum creatinine was 1.7 mg/dL (eGFR 40 mL/min/1.73m2) on last follow-up.

Discussion

We report 2 cases of progressive kidney disease in the setting of 225Ac-PSMA617 therapy for patients with advanced mCRPC. One underwent kidney biopsy showing tubulointerstitial injury, consistent with 225Ac-PSMA617-related tubular accumulation of toxic nuclides seen in animal models. This kidney injury was not responsive to corticosteroids therapy. Our case studies emphasized the need for careful assessment and monitoring of kidney function in patients receiving these novel agents.