Tolerability of PSMA radioligand therapy in metastatic prostate cancer patients with baseline mild to moderate leukopenia

TL;DR

This study shows that PSMA radioligand therapy is safe for prostate cancer patients with mild to moderate leukopenia, with no significant worsening of blood cell counts.

Contribution

The study demonstrates that PSMA-RLT can be safely administered to mCRPC patients with preexisting mild to moderate leukopenia.

Findings

Leukocyte counts remained stable after each PSMA-RLT cycle without significant deterioration.

Patients with leukopenia showed no significant change in CTCAE scores after treatment.

PSMA-RLT was feasible in patients with leukopenia, challenging its exclusion as a contraindication.

Abstract

Aim of this study was to analyze the safety of prostate-specific membrane antigen radioligand therapy (PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) with preexisting mild to moderate leukopenia (CTCAE ≥ 1).

Thirty-seven mCRPC patients with preexisting leukopenia (leukocyte count < 3.8 × 109/L) were included in this study. Patients received a median of 3 cycles of [177Lu]Lu-PSMA-617 (range 1–9). No significant difference in leukocyte counts was observed between baseline and follow-up after each PSMA-RLT cycle: first cycle (3.0 ± 0.5 at baseline vs. 3.4 ± 1.4 at follow up [in × 109/L], p = 0.0921), second cycle (3.1 ± 0.4 vs. 3.8 ± 1.7, p = 0. 0.0509), and third cycle (3.1 ± 0.4 vs. 3.2 ± 2.0, p = 0.2929), respectively. Similarly, baseline and end of treatment values, irrespective of the number of administered cycles, did not reveal a significant difference (3.0 ± 0.5 vs. 3.5 ± 1.4, p = 0.0684). After the end of therapy, irrespective of the number of administered cycles, 27% patients remained stable in terms of CTCAE scoring, 46% changed to a higher score and 27% improved to a lower score.

Although marked preexisting leukopenia is often considered a relative contraindication for PSMA-RLT, our findings indicate that PSMA-RLT is feasible in patients with leukopenia of CTCAE grade ≥ 1. In our cohort, leukocyte counts remained stable without significant RLT-induced deterioration. Therefore, patients with leukopenia should not be categorically excluded from receiving PSMA-RLT.

Trial registration: Clinicaltrials.gov identifier: NCT04833517, registered 01.01.2016.

The online version contains supplementary material available at 10.1186/s13550-025-01280-0.

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