TY  - JOUR
A1  - Gröner, Daniel
A1  - Nguyen, Cam Tu
A1  - Baumgarten, Justus
A1  - Bockisch, Benjamin
A1  - Davis, Karen
A1  - Happel, Christian
A1  - Mader, Nicolai
A1  - Nguyen Ngoc, Christina
A1  - Wichert, Jennifer
A1  - Banek, Séverine
A1  - Mandel, Philipp
A1  - Chun, Felix
A1  - Tselis, Nikolaos
A1  - Grünwald, Frank
A1  - Sabet, Amir
T1  - Hematologic safety of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
T2  - EJNMMI Research
N2  - 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.
KW  - PSMA
KW  - 177Lu-PSMA-617
KW  - Hematologic adverse events
KW  - Hematotoxicity
KW  - Metastatic castration-resistant prostate cancer
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63590
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-635902
SN  - 2191-219X
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 11
IS  - art. 61
SP  - 1
EP  - 11
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -