Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a...

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Autores: Mingot Castellano, María Eva, Reguera-Ortega, Juan Luis, Zafra Torres, Denis, Hernani, Rafael, Lopez-Godino, Oriana, Guerreiro, Manuel, Herrero, Blanca, Sanchez-Pina, Jose Maria, Spanish group of hematopoietic transplant and cell therapy Geth-Tc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:dnet:idus________::394061459a574355b47b2ba82312c8b0
Acceso en línea:https://hdl.handle.net/11441/185194
https://doi.org/10.3390/jcm13175117
Access Level:acceso abierto
Palabra clave:CAR-T
Adverse events
Eltrombopag
Neutropenia
Pan-cytopenia
Platelet transfusion
Red blood cell transfusion
Thrombocytopenia
Thrombopoietin receptor agonist
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spelling Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patientsMingot Castellano, María EvaReguera-Ortega, Juan LuisZafra Torres, DenisHernani, RafaelLopez-Godino, OrianaGuerreiro, ManuelHerrero, BlancaSanchez-Pina, Jose MariaSpanish group of hematopoietic transplant and cell therapy Geth-TcCAR-TAdverse eventsEltrombopagNeutropeniaPan-cytopeniaPlatelet transfusionRed blood cell transfusionThrombocytopeniaThrombopoietin receptor agonistBackground/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.MDPIMedicina2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/185194https://doi.org/10.3390/jcm13175117reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of clinical medicine, 13 (17), 5117. https://www.mdpi.com/2077-0383/13/17/5117info:eu-repo/semantics/openAccessoai:dnet:idus________::394061459a574355b47b2ba82312c8b02026-06-17T12:51:07Z
dc.title.none.fl_str_mv Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
title Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
spellingShingle Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
Mingot Castellano, María Eva
CAR-T
Adverse events
Eltrombopag
Neutropenia
Pan-cytopenia
Platelet transfusion
Red blood cell transfusion
Thrombocytopenia
Thrombopoietin receptor agonist
title_short Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
title_full Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
title_fullStr Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
title_full_unstemmed Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
title_sort Use of eltrombopag to improve thrombocytopenia and tranfusion requirement in anti-CD19 CAR-T cell-treated patients
dc.creator.none.fl_str_mv Mingot Castellano, María Eva
Reguera-Ortega, Juan Luis
Zafra Torres, Denis
Hernani, Rafael
Lopez-Godino, Oriana
Guerreiro, Manuel
Herrero, Blanca
Sanchez-Pina, Jose Maria
Spanish group of hematopoietic transplant and cell therapy Geth-Tc
author Mingot Castellano, María Eva
author_facet Mingot Castellano, María Eva
Reguera-Ortega, Juan Luis
Zafra Torres, Denis
Hernani, Rafael
Lopez-Godino, Oriana
Guerreiro, Manuel
Herrero, Blanca
Sanchez-Pina, Jose Maria
Spanish group of hematopoietic transplant and cell therapy Geth-Tc
author_role author
author2 Reguera-Ortega, Juan Luis
Zafra Torres, Denis
Hernani, Rafael
Lopez-Godino, Oriana
Guerreiro, Manuel
Herrero, Blanca
Sanchez-Pina, Jose Maria
Spanish group of hematopoietic transplant and cell therapy Geth-Tc
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
dc.subject.none.fl_str_mv CAR-T
Adverse events
Eltrombopag
Neutropenia
Pan-cytopenia
Platelet transfusion
Red blood cell transfusion
Thrombocytopenia
Thrombopoietin receptor agonist
topic CAR-T
Adverse events
Eltrombopag
Neutropenia
Pan-cytopenia
Platelet transfusion
Red blood cell transfusion
Thrombocytopenia
Thrombopoietin receptor agonist
description Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/185194
https://doi.org/10.3390/jcm13175117
url https://hdl.handle.net/11441/185194
https://doi.org/10.3390/jcm13175117
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of clinical medicine, 13 (17), 5117.
https://www.mdpi.com/2077-0383/13/17/5117
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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