Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients
Por:
Mingot-Castellano ME, Reguera-Ortega JL, Zafra Torres D, Hernani R, Lopez-Godino O, Guerreiro M, Herrero B, López-Corral L, Luna A, Gonzalez-Pinedo L, Chinea-Rodriguez A, Africa-Martín A, Bailen R, Martinez-Cibrian N, Balsalobre P, Filaferro S, Alonso-Saladrigues A, Barba P, Perez-Martinez A, Calbacho M, Perez-Simón JA, Sánchez-Pina JM, On Behalf Of The Spanish Group Of Hematopoietic Transplant And Cell Therapy Get
Publicada:
1 sep 2024
Ahead of Print:
28 ago 2024
Resumen:
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 x 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.
Filiaciones:
Mingot-Castellano ME:
Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/CSIC, Universidad de Sevilla, 41004 Sevilla, Spain
Reguera-Ortega JL:
Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/CSIC, Universidad de Sevilla, 41004 Sevilla, Spain
Zafra Torres D:
Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
Hernani R:
INCLIVA Health Research Institute, Hospital Clínico Universitario, 46010 Valencia, Spain
Lopez-Godino O:
Hematology Department, Centro Regional de Hemodonación, IMIB-Pascual Parrilla, Hospital Universitario Morales-Meseguer, 30008 Murcia, Spain
Guerreiro M:
Servicio de Hematología, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Herrero B:
Hospital Infantil Universitario del Niño Jesús, 28009 Madrid, Spain
López-Corral L:
IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Hospital Universitario de Salamanca (Spain), 37007 Salamanca, Spain
Luna A:
Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
Gonzalez-Pinedo L:
Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Spain
Chinea-Rodriguez A:
Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
Africa-Martín A:
IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Hospital Universitario de Salamanca (Spain), 37007 Salamanca, Spain
Bailen R:
Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain
Martinez-Cibrian N:
Hospital Clinic Barcelona, Institut de Recerca Sant Joan de Déu, Barcelona Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Balsalobre P:
University Hospital Vall d'Hebron, 08035 Barcelona, Spain
Filaferro S:
University Hospital Vall d'Hebron, 08035 Barcelona, Spain
Alonso-Saladrigues A:
Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Barba P:
Grupo Español de Trasplante Hematopoyético y Terapia Celular, 28040 Madrid, Spain
Perez-Martinez A:
Pediatric Hematology-Oncology Department, La Paz University Hospital, 28034 Madrid, Spain
Pediatric Department, Autonomous University of Madrid, 28034 Madrid, Spain
CIBERER-ISCIII, IdiPAZ-CNIO Pediatric OncoHematology Clinical Research Unit, 28034 Madrid, Spain
Calbacho M:
Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
Perez-Simón JA:
Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/CSIC, Universidad de Sevilla, 41004 Sevilla, Spain
Sánchez-Pina JM:
Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
On Behalf Of The Spanish Group Of Hematopoietic Transplant And Cell Therapy Get:
Grupo Español de Trasplante Hematopoyético y Terapia Celular, 28040 Madrid, Spain
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