Hematologic safety of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer

Daniel Groener; Cam Tu Nguyen; Justus Baumgarten; Benjamin Bockisch; Karen Davis; Christian Happel; Nicolai Mader; Christina Nguyen Ngoc; Jennifer Wichert; Severine Banek; Philipp Mandel; Felix K H Chun; Nikolaos Tselis; Frank Grünwald; Amir Sabet

doi:10.1186/s13550-021-00805-7

Hematologic safety of ¹⁷⁷Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer

EJNMMI Res. 2021 Jul 3;11(1):61. doi: 10.1186/s13550-021-00805-7.

Authors

Affiliations

¹ Department of Nuclear Medicine, University Hospital Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
² Department of Urology, University Hospital Frankfurt, Frankfurt, Germany.
³ Department of Radiation Oncology, University Hospital Frankfurt, Frankfurt, Germany.
⁴ Department of Nuclear Medicine, University Hospital Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt, Germany. amir.sabet@kgu.de.

Abstract

Background: Myelosuppression is a potential dose-limiting factor in radioligand therapy (RLT). This study aims to investigate occurrence, severity and reversibility of hematotoxic adverse events in patients undergoing RLT with ¹⁷⁷Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC). The contribution of pretreatment risk factors and cumulative treatment activity is taken into account specifically.

Methods: RLT was performed in 140 patients receiving a total of 497 cycles. A mean activity of 6.9 [Formula: see text] 1.3 GBq ¹⁷⁷Lu-PSMA-617 per cycle was administered, and mean cumulative activity was 24.6 [Formula: see text] 15.9 GBq. Hematological parameters were measured at baseline, prior to each treatment course, 2 to 4 weeks thereafter and throughout follow-up. Toxicity was graded based on Common Terminology Criteria for Adverse Events v5.0.

Results: Significant (grade ≥ 3) hematologic adverse events occurred in 13 (9.3%) patients, with anemia in 10 (7.1%), leukopenia in 5 (3.6%) and thrombocytopenia in 6 (4.3%). Hematotoxicity was reversible to grade ≤ 2 through a median follow-up of 8 (IQR 9) months in all but two patients who died from disease progression within less than 3 months after RLT. Myelosuppression was significantly more frequent in patients with pre-existing grade 2 cytopenia (OR: 3.50, 95%CI 1.08-11.32, p = 0.04) or high bone tumor burden (disseminated or diffuse based on PROMISE miTNM, OR: 5.08, 95%CI 1.08-23.86, p = 0.04). Previous taxane-based chemotherapy was associated with an increased incidence of significant hematotoxicity (OR: 4.62, 95%CI 1.23-17.28, p = 0.02), while treatment with ²²³Ra-dichloride, cumulative RLT treatment activity and activity per cycle were not significantly correlated (p = 0.93, 0.33, 0.29).

Conclusion: Hematologic adverse events after RLT have an acceptable overall incidence and are frequently reversible. High bone tumor burden, previous taxane-based chemotherapy and pretreatment grade 2 cytopenia may be considered as risk factors for developing clinically relevant myelosuppression, whereas cumulative RLT activity and previous ²²³Ra-dichloride treatment show no significant contribution to incidence rates.

Keywords: 177Lu-PSMA-617; Hematologic adverse events; Hematotoxicity; Metastatic castration-resistant prostate cancer; PSMA.