Siltuximab for the treatment of early complications after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia in children, adolescents, and young adults.

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 retrosp...

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Detalles Bibliográficos
Autores: Galán-Gómez V, González-Martínez B, Alonso-Saladrigues A, Rives 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, Pérez-Martínez A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p28448
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28448
Access Level:acceso abierto
Palabra clave:Chimeric antigen receptor—CAR
Cytokine release syndrome
Immune effector cell-associated neurotoxicity syndrome—ICANS
Leukemia
Neurotoxicity
Siltuximab
Tocilizumab
Descripción
Sumario: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.