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Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer

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Abstract

Purpose

Actinium-225-labeled prostate-specific membrane antigen ([225Ac]Ac-PSMA-617) is safe and effective in the treatment of metastatic castration-resistant prostate cancer (mCRPC). No study has specifically assessed its safety in patients with extensive skeletal metastases of mCRPC. We aimed to investigate the hematologic toxicity and efficacy of [225Ac]Ac-PSMA-617 therapy in patients with extensive skeletal metastases of mCRPC.

Methods

We retrospectively reviewed the medical record of patients treated with [225Ac]Ac-PSMA-617 for mCRPC. We included patients with a superscan pattern of skeletal metastases and those with 20 or more multifocal sites of skeletal metastases on baseline [68 Ga]Ga-PSMA-11 PET/CT. We reviewed the levels of hemoglobin, white blood cell (WBC), and platelet prior to each cycle of treatment and determined the presence of impaired bone marrow function at baseline and the grade of toxicity in the hematologic parameters induced by treatment. We evaluated the predictors of hematologic toxicity using binary logistic regression analysis. We also determined the presence of renal dysfunction before or during treatment. We assessed response to treatment using prostate-specific antigen response and the progression-free survival (PFS) and overall survival (OS).

Results

A total of 106 patients were included. Skeletal metastasis was in the superscan pattern in 34 patients (32.1%) and multifocal in 72 patients (67.9%). The median treatment cycle was 4 (range = 1–9). Ninety-eight patients (92.5%) had abnormal baseline hematologic parameters. One patient had grade 4 thrombocytopenia. Grade 3 anemia, leukopenia, and thrombocytopenia were seen in 1 (0.9%), 3 (2.8%), and 2 (1.9%) patients, respectively. Age, the number of treatment cycles, and the presence of renal dysfunction were significant predictors of hematologic toxicity. Eighty-five patients (80.2%) achieved PSA response. The median PFS and OS of the study population were 14:00 (95%CI: 8.15–19.86) months and 15.0 (95%CI: 12.8–17.2) months, respectively.

Conclusions

[225Ac]Ac-PSMA-617 induces a good anti-tumor effect in about 80% of patients with extensive skeletal metastases of mCRPC with a rare incidence of severe hematologic toxicity. Age, number of treatment cycles, and the presence of renal dysfunction were significant risk factors for hematologic toxicity of [225Ac]Ac-PSMA-617 therapy.

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Data availability

All data collected during the conduct of this study are included in this report.

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Authors and Affiliations

  1. Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa

    Ismaheel O. Lawal, Kgomotso M. G. Mokoala, Amanda Mdlophane & Mike M. Sathekge

  2. Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa

    Ismaheel O. Lawal, Johncy Mahapane, Khanyisile N. Hlongwa, Letjie C. Maserumule, Honest Ndlovu, Janet D. Reed, Kgomotso M. G. Mokoala, Amanda Mdlophane & Mike M. Sathekge

  3. Joint Research Centre, Directorate for Nuclear Safety and Security, European Commission, 0001, Karlsruhe, Germany

    Alfred Morgenstern & Frank Bruchertseifer

  4. Department of Nuclear Medicine, University of Kwa-Zulu Natal & Inkosi Albert Lithuli Central Academic Hospital, Durban, South Africa

    Mariza Vorster

  5. Nuclear Technology Products (NTP), Pelindaba, South Africa

    Otto Knoesen

  6. Department of Radiography, University of Pretoria, Pretoria, South Africa

    Johncy Mahapane

  7. Saxon Court Lincolnshire Partnership NHS Foundation Trust (LPFT), Lincoln, Lincolnshire, UK

    Gbenga O. Popoola

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  1. Ismaheel O. Lawal
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  2. Alfred Morgenstern
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Correspondence to Mike M. Sathekge.

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Lawal, I.O., Morgenstern, A., Vorster, M. et al. Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 49, 3581–3592 (2022). https://doi.org/10.1007/s00259-022-05778-w

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