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

  • 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 ± 1.3 GBq 177Lu-PSMA-617 per cycle was administered, and mean cumulative activity was 24.6 ± 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.

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Author:Daniel GrönerORCiDGND, Cam Tu NguyenGND, Justus BaumgartenGND, Benjamin Bockisch, Karen Davis, Christian HappelORCiDGND, Nicolai MaderORCiDGND, Christina Nguyen Ngoc, Jennifer WichertGND, Séverine BanekGND, Philipp MandelORCiDGND, Felix ChunORCiDGND, Nikolaos TselisGND, Frank GrünwaldGND, Amir SabetORCiDGND
Parent Title (English):EJNMMI Research
Place of publication:Berlin ; Heidelberg
Document Type:Article
Date of Publication (online):2021/07/03
Date of first Publication:2021/07/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/05/10
Tag:177Lu-PSMA-617; Hematologic adverse events; Hematotoxicity; Metastatic castration-resistant prostate cancer; PSMA
Issue:art. 61
Page Number:11
First Page:1
Last Page:11
Open Access funding enabled and organized by Projekt DEAL.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0