Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative Lu-177-DOTAGA-(I-y)fk(Sub-KuE) (Lu-177-PSMA I&T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography ( Ga-68-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade >= 3 haematologic toxicity, including association with risk factors (age >= 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of Lu-177 PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50-89), median number of prior therapies was three (1-6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p < 0.0001; 95% CI: 0.08-0.44). Regarding haematologic toxicity, 11% experienced a grade >= 3 cytopenia (self-limiting). No cases of myelodysplasia /acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: Lu-177-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. Ga-68-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.