Siltuximab for the treatment of early complications after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia in children, adolescents, and young adults.
Por:
Galán-Gómez V, González-Martínez B, Alonso-Saladrigues A, Rives-Solà S, Herrero B, Kwon M, Sánchez-Pina J, Minguillón J, Martínez-Romera I, Mirones Aguilar I, Mestre-Durán C, Casado G, Sánchez-Martín M, Echecopar C, González-Pérez C, León-Triana O, Aguirre-Portolés C, Molinos-Quintana Á, Barba P, Balsalobre P and Pérez-Martínez A
Publicada:
2 abr 2025
Ahead of Print:
2 abr 2025
Resumen:
BACKGROUND: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are complications associated with CAR T-cell therapy. Siltuximab directly binds interleukin-6 (IL-6) and may be safe and effective as first-line therapy for CRS or ICANS. METHODS: A retrospective study was conducted on pediatric, adolescent and young adult (AYA) patients treated with siltuximab after CAR T-cell therapy for B-ALL. RESULTS: A total of 118 patients treated were included: 97 patients developed CRS (82%), and 26 patients (22%) developed ICANS. Sixty-five of those that developed CRS (55%), received treatment. In 46/65 (71%), tocilizumab was administered as anti-IL-6 drug, and 19/65 (29%) patients received siltuximab to treat tocilizumab-refractory CRS (n = 13, 68%), or as first-line CRS treatment (n = 6, 32%). Nine patients treated with siltuximab (47%) developed ICANS. With a median follow-up of 12.1 months, 7 patients remained alive. CONCLUSIONS: To the best of our knowledge, we present the largest reported cohort of patients treated with siltuximab for CRS following CAR T-cell therapy for B-ALL. Siltuximab's safety profile and its inhibition of IL-6 effects suggest that it should be investigated as first-line therapy in prospective clinical trials.
Filiaciones:
Galán-Gómez V:
Pediatric Hemato-Oncology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain
CIBERER-ISCIII, IdiPAZ-CNIO Pediatric Onco-Hematology Clinical Research Unit, Madrid, Spain
González-Martínez B:
Pediatric Hemato-Oncology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain
Alonso-Saladrigues A:
Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu, Barcelona, Spain
CIBERER-ISCIII, Sant Joan de Déu Research Institute, Barcelona, Spain
Rives-Solà S:
Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu, Barcelona, Spain
CIBERER-ISCIII, Sant Joan de Déu Research Institute, Barcelona, Spain
Herrero B:
Pediatric Hemato-Oncology Department, Pediatric University Hospital del Niño Jesús, Madrid, Spain
Kwon M:
Hematology and Hemotherapy Department, Gregorio Marañón Health Research Institute, General University Hospital Gregorio Marañón, Madrid, Spain
Sánchez-Pina J:
Hematology and Hemotherapy Department, University Hospital 12 de Octubre, Madrid, Spain
Minguillón J:
CIBERER-ISCIII, IdiPAZ-CNIO Pediatric Onco-Hematology Clinical Research Unit, Madrid, Spain
Advanced Therapies Mixed Unit, CIEMAT/IIS-FJD, Madrid, Spain
Martínez-Romera I:
Pediatric Hemato-Oncology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain
Mirones Aguilar I:
Advanced Therapy Medicinal Products Production Unit, La Paz University Hospital, Madrid, Spain
Mestre-Durán C:
CIBERER-ISCIII, IdiPAZ-CNIO Pediatric Onco-Hematology Clinical Research Unit, Madrid, Spain
Casado G:
Pharmacy Department, La Paz University Hospital, Madrid, Spain
Sánchez-Martín M:
Pediatric Intensive Care Department, La Paz University Hospital, Madrid, Spain
Echecopar C:
Pediatric Hemato-Oncology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain
González-Pérez C:
Pediatric Hemato-Oncology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain
León-Triana O:
Biostatistics Unit, Institute for Health Research (IdiPAZ), Madrid, Spain
Aguirre-Portolés C:
CIBERER-ISCIII, IdiPAZ-CNIO Pediatric Onco-Hematology Clinical Research Unit, Madrid, Spain
Molinos-Quintana Á:
Hematology Department, Hospital Virgen del Rocío, Seville, Spain
Barba P:
Hematology Department, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
Balsalobre P:
Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC), Madrid, Spain
Pérez-Martínez A:
Pediatric Hemato-Oncology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain
CIBERER-ISCIII, IdiPAZ-CNIO Pediatric Onco-Hematology Clinical Research Unit, Madrid, Spain
Advanced Therapy Medicinal Products Production Unit, La Paz University Hospital, Madrid, Spain
Pediatric Department, Autonomous University of Madrid, Madrid, Spain
Green Submitted, gold
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