177-Lu-PSMA-617 in a patient with stage 4 chronic kidney disease

Introduction: ¹⁷⁷Lu-PSMA-617 was approved by the FDA based on the results of the VISION trial. Current prescribing guidelines recommend withholding the treatment if creatinine clearance (via Cockcroft-Gault calculation) is < 30 mL/min based on the VISION trial exclusion criteria. Patients with CrCl < 50 mL/min or Cr > 1.5 x ULN were excluded because the renal tubules express a small amount of prostate-specific membrane antigen, raising concerns for potential renal toxicity of ¹⁷⁷Lu-PSMA-617 on already impaired renal function. Several studies have since shown variable effects of ¹⁷⁷Lu-PSMA-617 radiation on the kidneys, but to date, no studies have investigated outcomes of patients with stage 4 chronic kidney disease (CKD-4). We report a single patient’s response to four cycles of ¹⁷⁷Lu-PSMA-617 treatment with a history of CKD-4.

Methods: A single patient with CKD-4 who had undergone ¹⁷⁷Lu-PSMA-617 treatment after failure of other therapies was retrospectively selected. Electronic medical records were reviewed to evaluate patient’s prior therapies, including but not limited to local therapy, androgen deprivation therapy, and chemotherapy. Blood work, including CBC and BMP, was drawn before treatment and every two weeks during therapy as per institutional protocol.

Results: An 80-year-old man presented with metastatic castration-resistant prostate cancer with lymph node only metastases and CKD-4. He had undergone radical prostatectomy, androgen receptor therapy, and one cycle of docetaxel chemotherapy which was terminated due to life-threatening gastrointestinal bleeding. Due to his refusal of further taxane-based chemotherapy and lack of other standard options, ¹⁷⁷Lu-PSMA-617 therapy was initiated. Before starting this therapy, PSA was 34.1 ng/mL, serum creatinine was 2.9 mg/dL, and creatinine clearance was 21 mL/min.

After three cycles of treatment, the patient has responded well in terms of disease burden as evaluated by decline in PSA, with a value of 3.9 ng/mL just before his fourth cycle (an 88.6% decrease). His CrCl remains stable at 22 mL/min from a baseline of 21 mL/min, and his serum creatinine remains stable at 2.8 mg/dL from a baseline of 2.9 mg/dL. He has just received his fourth cycle, and because of his favorable response to treatment and stable renal function, ¹⁷⁷Lu-PSMA-617 treatment will be extended for a full 6 cycles provided that laboratory testing confirms continued intact bone marrow and kidney function.

Conclusions: In this report, we demonstrate that a patient with metastatic castration-resistant prostate cancer and CKD-4 tolerated 4 cycles of ¹⁷⁷Lu-PSMA-617 treatment with no deleterious effects on his baseline renal function. While more research is needed to rule out delayed-onset kidney injury, this single case suggests that the patient with end stage renal disease can be safety and effectively treated with 177Lu-PSMA-617 without causing further near-term renal impairment.