Safety profile of lutetium-177 in patients with impaired renal function: A retrospective analysis of adverse events in mCRPC treatment.

123 Background: Lutetium-177 vipivotide tetraxetan (Lu177) is the first FDA-approved radioligand therapy for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Not much is known regarding the safety of dosing of Lu177 in patients with creatinine clearance outside the range included in VISION trial (Sartor et al.) which was ≥50 mL/min. Using an institutional database of patients treated with Lu177, we sought to analyze whether there were increased incidences of adverse events (AEs) in patients with impaired renal function who received Lu177. Methods: We retrospectively identified 58 patients with mCRPC who received Lu177 from 2022 - 2024 at a single center (City of Hope). Impaired renal function was defined as an eGFR ≤ 60 mL/min prior to initiation of Lu177 and not confounded by acute renal injury. Statistical analysis was performed using R (v.4.4.1). A Fisher’s Exact test was used to determine whether impaired renal function was associated with increased frequency of AEs. Results: Among the 58 patients, 28 (48.28%) were Caucasian/White, 19 (32.76%) were Latino/Hispanic, 6 (10.34%) were African American/Black, and 5 (8.62%) were Asian/Pacific Islander. Median age was 68.5 years old (40-86 years old). There were 6 patients with low GFR (37 to 60 ml/min) and 36 patients with normal GFR >60 mL/min. Both groups received standard pluvicto doses. In terms of AEs, the most common AEs were anemia (41.54%), thrombocytopenia (12.31%), xerostomia (10.77%), and fatigue (10.77%). For G3/G4 AEs, the most common were anemia (56.25%) and thrombocytopenia (18.75%). Only one patient with prior impaired renal function (GFR <60 mL/min) experienced deterioration of renal function. There was no significant difference noted in incidence of AEs, incidence of anemia, and incidence of G3/G4 anemia between those with impaired renal function and those with normal function (p = 1, p = 0.7119, p = 0.6649 respectively). Conclusions: Patients with GFR < 60 mL/min did not identify an increased incidence of AEs, including anemia, when treated with Lu177. Patients with impaired GFR experienced a similar AE profile (anemia, thrombocytopenia, and xerostomia) as described in prior data sets. Our findings suggest that Lu177 may be safely dosed in patients with impaired renal function as low as eGFR 37 mL/min, without significantly increasing the risk of AEs.