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

Murali Kesavan; Danielle Meyrick; Marat Gallyamov; J Harvey Turner; Sharon Yeo; Giuseppe Cardaci; Nat P Lenzo

doi:10.3390/diagnostics11030515

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

Diagnostics (Basel). 2021 Mar 14;11(3):515. doi: 10.3390/diagnostics11030515.

Authors

Murali Kesavan^{1

2}, Danielle Meyrick², Marat Gallyamov³, J Harvey Turner², Sharon Yeo³, Giuseppe Cardaci⁴, Nat P Lenzo^{3

4}

Affiliations

¹ Department of Haematology, School of Medicine, The University of Western Australia, Perth 6009, Australia.
² Department of Nuclear Medicine, School of Medicine, The University of Western Australia, Perth 6009, Australia.
³ GenesisCare, East Fremantle, Fremantle 6158, Australia.
⁴ School of Medicine, The University of Notre Dame, Fremantle 6160, Australia.

Abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (¹⁷⁷Lu-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 ¹⁷⁷Lu-DOTAGA-(I-y)fk(Sub-KuE) (¹⁷⁷Lu-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 (⁶⁸Ga-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 ¹⁷⁷Lu 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: ¹⁷⁷Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. ⁶⁸Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.

Keywords: LuPSMA; MDS; hematologic toxicity; mCRPC.