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2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a rapidly evolving immunotherapy for hematological malignancies. With increasing access to this modality, there is an urgent need for a comprehensive understanding of infectious complications to optimize prophylaxis and improve clinical o...

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Autores principales: Banegas, Marcela, Bindal, Poorva, Woodbine, Maria Jose Hernandez, Aggarwal, Pushan, Paredes, Rodrigo, Arnason, Jon, Alonso, Carolyn D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10677339/
http://dx.doi.org/10.1093/ofid/ofad500.2305
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author Banegas, Marcela
Bindal, Poorva
Woodbine, Maria Jose Hernandez
Aggarwal, Pushan
Paredes, Rodrigo
Arnason, Jon
Alonso, Carolyn D
author_facet Banegas, Marcela
Bindal, Poorva
Woodbine, Maria Jose Hernandez
Aggarwal, Pushan
Paredes, Rodrigo
Arnason, Jon
Alonso, Carolyn D
author_sort Banegas, Marcela
collection PubMed
description BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a rapidly evolving immunotherapy for hematological malignancies. With increasing access to this modality, there is an urgent need for a comprehensive understanding of infectious complications to optimize prophylaxis and improve clinical outcomes. We conducted a meta-analysis to assess the incidence and types of infectious complications in adult patients receiving CAR T-cell therapy. METHODS: The study was registered on PROSPERO and we searched 5 electronic databases from inception to 2022. Each author independently screened titles, reviewed full texts to identify eligible studies and extracted data from included studies using Covidence, a data extraction tool for conduction of standard systematic reviews. A random effects model was used, and proportions were used as a measure of outcome. We assessed heterogeneity using I^2 statistic. Risk of bias assessments were conducted using the RoB 2.0 for RCTs and ROBINS I tool for non-RCTs. RESULTS: Our search identified 12,441 studies of which 363 underwent full-text review. 33 studies were eligible for inclusion in the analysis and enrolled a total of 2866 patients. The pooled incidence of an infectious event in adult patients after CAR T-cell therapy was 38% (95%CI 0.31, 0.46; p< 0.01; I2 = 98%]. No significant difference was noted in the incidence among studies with a longer follow up duration compared to studies with follow up of ≤ 30 days [40% (95% CI 0.30-0.50) vs 32% (95% CI 0.24-0.40), p=0.20 respectively]. BCMA-directed CAR T-cell therapies used for management of multiple myeloma had a significantly higher incidence of infectious complications compared to CD19 targeted agents, 64% (95% CI 0.53-0.74, I2 = 65%) versus 39% (95% CI 0.30-0.49; I2 = 98%; p < 0.01) respectively, Figure 1. Clostridium difficile and Escherichia coli were the most common pathogens causing bacterial infections, while cytomegalovirus was the most commonly identified viral pathogen. Figure 1. [Figure: see text] Subgroup analysis of the pooled incidence of infectious events after CAR T-cell therapy among adult patients with hematologic malignancies CONCLUSION: In this study, BCMA-directed CAR T-cell therapies were associated with a significantly higher risk of infectious complications. The results of this study can guide the development of strategies to prevent and manage infectious complications in this patient population. DISCLOSURES: Jon Arnason, MD, BMS: Advisor/Consultant|Regeneron: Advisor/Consultant Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support
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spelling pubmed-106773392023-11-27 2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis Banegas, Marcela Bindal, Poorva Woodbine, Maria Jose Hernandez Aggarwal, Pushan Paredes, Rodrigo Arnason, Jon Alonso, Carolyn D Open Forum Infect Dis Abstract BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a rapidly evolving immunotherapy for hematological malignancies. With increasing access to this modality, there is an urgent need for a comprehensive understanding of infectious complications to optimize prophylaxis and improve clinical outcomes. We conducted a meta-analysis to assess the incidence and types of infectious complications in adult patients receiving CAR T-cell therapy. METHODS: The study was registered on PROSPERO and we searched 5 electronic databases from inception to 2022. Each author independently screened titles, reviewed full texts to identify eligible studies and extracted data from included studies using Covidence, a data extraction tool for conduction of standard systematic reviews. A random effects model was used, and proportions were used as a measure of outcome. We assessed heterogeneity using I^2 statistic. Risk of bias assessments were conducted using the RoB 2.0 for RCTs and ROBINS I tool for non-RCTs. RESULTS: Our search identified 12,441 studies of which 363 underwent full-text review. 33 studies were eligible for inclusion in the analysis and enrolled a total of 2866 patients. The pooled incidence of an infectious event in adult patients after CAR T-cell therapy was 38% (95%CI 0.31, 0.46; p< 0.01; I2 = 98%]. No significant difference was noted in the incidence among studies with a longer follow up duration compared to studies with follow up of ≤ 30 days [40% (95% CI 0.30-0.50) vs 32% (95% CI 0.24-0.40), p=0.20 respectively]. BCMA-directed CAR T-cell therapies used for management of multiple myeloma had a significantly higher incidence of infectious complications compared to CD19 targeted agents, 64% (95% CI 0.53-0.74, I2 = 65%) versus 39% (95% CI 0.30-0.49; I2 = 98%; p < 0.01) respectively, Figure 1. Clostridium difficile and Escherichia coli were the most common pathogens causing bacterial infections, while cytomegalovirus was the most commonly identified viral pathogen. Figure 1. [Figure: see text] Subgroup analysis of the pooled incidence of infectious events after CAR T-cell therapy among adult patients with hematologic malignancies CONCLUSION: In this study, BCMA-directed CAR T-cell therapies were associated with a significantly higher risk of infectious complications. The results of this study can guide the development of strategies to prevent and manage infectious complications in this patient population. DISCLOSURES: Jon Arnason, MD, BMS: Advisor/Consultant|Regeneron: Advisor/Consultant Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support Oxford University Press 2023-11-27 /pmc/articles/PMC10677339/ http://dx.doi.org/10.1093/ofid/ofad500.2305 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
Banegas, Marcela
Bindal, Poorva
Woodbine, Maria Jose Hernandez
Aggarwal, Pushan
Paredes, Rodrigo
Arnason, Jon
Alonso, Carolyn D
2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
title 2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
title_full 2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
title_fullStr 2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
title_full_unstemmed 2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
title_short 2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
title_sort 2694. infectious complications in car-t cell therapy recipients: a systematic review and meta-analysis
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10677339/
http://dx.doi.org/10.1093/ofid/ofad500.2305
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