Abstract：
BACKGROUND: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy.
METHODS: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab.
RESULTS: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells.
CONCLUSIONS: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.
METHODS: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab.
RESULTS: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells.
CONCLUSIONS: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.
摘要：
背景：Tocilizumab通常用于治疗嵌合抗原受体（CAR）T细胞治疗相关的细胞因子释放综合征（CRS）。然而,托珠单抗或其剂量是否会影响CAR-T细胞治疗的疗效和安全性仍不得而知.这项多中心回顾性研究的目的是探讨托珠单抗对CAR-T细胞治疗的影响。
方法：总共，从2016年5月至2022年11月，招募了93例接受人源化抗CD19CART细胞治疗的B细胞急性淋巴细胞白血病（B-ALL）患者。45例患者接受托珠单抗（托珠单抗组），而48例患者没有（非托珠单抗组）。13例患者接受>1剂量的托珠单抗。主要终点是托珠单抗对CAR-T细胞功效和安全性的影响。此外,扩散,杀戮,和CART细胞的细胞因子测定在托珠单抗存在下在体外进行.
结果：患者的中位年龄为33岁，男性47人，女性46人。托珠单抗组患者表现出相似的完全缓解（CR）率，总生存期（OS），和无事件生存率（EFS）与非托珠单抗组相比。与接受≤1剂量托珠单抗的患者相比，接受>1剂量的托珠单抗并不影响他们的CR率，操作系统,或EFS。在托珠单抗组,所有患者均出现CRS,26.7%的患者出现免疫效应细胞相关神经毒性综合征(ICANS).在非托珠单抗组中，64.6%的患者经历过CRS，8.3%的患者经历过ICANS。高达75%的ICANS和87.5%的≥3级ICANS发生在托珠单抗组。体外，托珠单抗不会损害CAR-T细胞的增殖和杀伤作用.
结论：Tocilizumab不影响CAR-T细胞的疗效，但可能增加ICANS的可能性。
方法：总共，从2016年5月至2022年11月，招募了93例接受人源化抗CD19CART细胞治疗的B细胞急性淋巴细胞白血病（B-ALL）患者。45例患者接受托珠单抗（托珠单抗组），而48例患者没有（非托珠单抗组）。13例患者接受>1剂量的托珠单抗。主要终点是托珠单抗对CAR-T细胞功效和安全性的影响。此外,扩散,杀戮,和CART细胞的细胞因子测定在托珠单抗存在下在体外进行.
结果：患者的中位年龄为33岁，男性47人，女性46人。托珠单抗组患者表现出相似的完全缓解（CR）率，总生存期（OS），和无事件生存率（EFS）与非托珠单抗组相比。与接受≤1剂量托珠单抗的患者相比，接受>1剂量的托珠单抗并不影响他们的CR率，操作系统,或EFS。在托珠单抗组,所有患者均出现CRS,26.7%的患者出现免疫效应细胞相关神经毒性综合征(ICANS).在非托珠单抗组中，64.6%的患者经历过CRS，8.3%的患者经历过ICANS。高达75%的ICANS和87.5%的≥3级ICANS发生在托珠单抗组。体外，托珠单抗不会损害CAR-T细胞的增殖和杀伤作用.
结论：Tocilizumab不影响CAR-T细胞的疗效，但可能增加ICANS的可能性。
