Hematologic safety of (177)Lu-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 (177)Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCR...

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Autores principales: Groener, Daniel, Nguyen, Cam Tu, Baumgarten, Justus, Bockisch, Benjamin, Davis, Karen, Happel, Christian, Mader, Nicolai, Nguyen Ngoc, Christina, Wichert, Jennifer, Banek, Severine, Mandel, Philipp, Chun, Felix K. H., Tselis, Nikolaos, Grünwald, Frank, Sabet, Amir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254689/
https://www.ncbi.nlm.nih.gov/pubmed/34216290
http://dx.doi.org/10.1186/s13550-021-00805-7
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author Groener, Daniel
Nguyen, Cam Tu
Baumgarten, Justus
Bockisch, Benjamin
Davis, Karen
Happel, Christian
Mader, Nicolai
Nguyen Ngoc, Christina
Wichert, Jennifer
Banek, Severine
Mandel, Philipp
Chun, Felix K. H.
Tselis, Nikolaos
Grünwald, Frank
Sabet, Amir
author_facet Groener, Daniel
Nguyen, Cam Tu
Baumgarten, Justus
Bockisch, Benjamin
Davis, Karen
Happel, Christian
Mader, Nicolai
Nguyen Ngoc, Christina
Wichert, Jennifer
Banek, Severine
Mandel, Philipp
Chun, Felix K. H.
Tselis, Nikolaos
Grünwald, Frank
Sabet, Amir
author_sort Groener, Daniel
collection PubMed
description 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 (177)Lu-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 (177)Lu-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 (223)Ra-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 (223)Ra-dichloride treatment show no significant contribution to incidence rates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00805-7.
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spelling pubmed-82546892021-07-20 Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer Groener, Daniel Nguyen, Cam Tu Baumgarten, Justus Bockisch, Benjamin Davis, Karen Happel, Christian Mader, Nicolai Nguyen Ngoc, Christina Wichert, Jennifer Banek, Severine Mandel, Philipp Chun, Felix K. H. Tselis, Nikolaos Grünwald, Frank Sabet, Amir EJNMMI Res Original Research 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 (177)Lu-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 (177)Lu-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 (223)Ra-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 (223)Ra-dichloride treatment show no significant contribution to incidence rates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00805-7. Springer Berlin Heidelberg 2021-07-03 /pmc/articles/PMC8254689/ /pubmed/34216290 http://dx.doi.org/10.1186/s13550-021-00805-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research
Groener, Daniel
Nguyen, Cam Tu
Baumgarten, Justus
Bockisch, Benjamin
Davis, Karen
Happel, Christian
Mader, Nicolai
Nguyen Ngoc, Christina
Wichert, Jennifer
Banek, Severine
Mandel, Philipp
Chun, Felix K. H.
Tselis, Nikolaos
Grünwald, Frank
Sabet, Amir
Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
title Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
title_full Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
title_fullStr Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
title_full_unstemmed Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
title_short Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
title_sort hematologic safety of (177)lu-psma-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254689/
https://www.ncbi.nlm.nih.gov/pubmed/34216290
http://dx.doi.org/10.1186/s13550-021-00805-7
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