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. 2025 Apr 2;14(1):49.
doi: 10.1186/s40164-025-00638-3.

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

Víctor Galán-Gómez  1   2 , Berta González-Martínez  1 , Anna Alonso-Saladrigues  3   4 , Susana Rives  3   4 , Blanca Herrero  5 , Mi Kwon  6 , Jose Sánchez-Pina  7 , Jordi Minguillón  2   8 , Isabel Martínez-Romera  1 , Isabel Mirones Aguilar  9 , Carmen Mestre-Durán  2 , Gema Casado  10 , María Sánchez-Martín  11 , Carlos Echecopar  1 , Carlos González-Pérez  1 , Odelaisy León-Triana  12 , Cristina Aguirre-Portolés  2 , Águeda Molinos-Quintana  13 , Pere Barba  14 , Pascual Balsalobre  15 , Antonio Pérez-Martínez  16   17   18   19
Affiliations

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

Víctor Galán-Gómez et al. Exp Hematol Oncol. .

Abstract

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.

Keywords: Chimeric antigen receptor—CAR; Cytokine release syndrome; Immune effector cell-associated neurotoxicity syndrome—ICANS; Leukemia; Neurotoxicity; Siltuximab; Tocilizumab.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Institutional Review Board of La Paz University Hospital approved the study, and it was ratified by all participating centers (PI5630). The study was conducted in accordance with the Declaration of Helsinki (latest version, Fortaleza 2013), as well as with Spanish and EU laws and regulations applicable to observational studies. Written informed consent was obtained from the patients’ parents before data collection. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Swimmer plot of CRS/ICANS management and outcomes after CAR T-cell therapy
Fig. 2
Fig. 2
Flow chart of patients who received siltuximab
See this image and copyright information in PMC

References

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