Galán-Gómez Víctor, González-Martínez Berta, Alonso-Saladrigues Anna, Rives Susana, Herrero Blanca, Kwon Mi, Sánchez-Pina Jose, Minguillón Jordi, Martínez-Romera Isabel, Mirones Aguilar Isabel, Mestre-Durán Carmen, Casado Gema, Sánchez-Martín María, Echecopar Carlos, González-Pérez Carlos, León-Triana Odelaisy, Aguirre-Portolés Cristina, Molinos-Quintana Águeda, Barba Pere, Balsalobre Pascual, Pérez-Martínez Antonio
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.
Exp Hematol Oncol. 2025 Apr 2;14(1):49. doi: 10.1186/s40164-025-00638-3.
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.
A retrospective study was conducted on pediatric, adolescent and young adult (AYA) patients treated with siltuximab after CAR T-cell therapy for B-ALL.
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.
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.
细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）是嵌合抗原受体T细胞（CAR T）疗法的并发症。西妥昔单抗直接结合白细胞介素-6（IL-6），可能作为CRS或ICANS的一线治疗安全有效。
对接受CAR T细胞疗法治疗B淋巴细胞白血病（B-ALL）后接受西妥昔单抗治疗的儿童、青少年和青年（AYA）患者进行了一项回顾性研究。
共纳入118例接受治疗的患者：97例发生CRS（82%），26例（22%）发生ICANS。发生CRS的患者中有65例（55%）接受了治疗。在65例患者中的46例（71%）中，托珠单抗作为抗IL-6药物给药，19例（29%）患者接受西妥昔单抗治疗难治性CRS（n = 13，68%），或作为一线CRS治疗（n = 6，32%）。9例接受西妥昔单抗治疗的患者（47%）发生ICANS。中位随访12.1个月，7例患者存活。
据我们所知，我们报告了接受CAR T细胞疗法治疗B-ALL后使用西妥昔单抗治疗CRS的最大队列患者。西妥昔单抗的安全性及其对IL-6效应的抑制表明，应在前瞻性临床试验中将其作为一线治疗进行研究。
