Impact of tocilizumab on anti-CD19 chimeric antigen receptor T-cell therapy in B-cell acute lymphoblastic leukemia

Xiangmin Wang; Bingpei Zhang; Qing Zhang; Hongyuan Zhou; Qian Sun; Yi Zhou; Tianci Li; Dian Zhou; Ziyuan Shen; Jiaoli Zhang; Ping Li; Aibin Liang; Keshu Zhou; Lu Han; Yongxian Hu; Yun Yang; Jiang Cao; Zhenyu Li; Kailin Xu; Wei Sang

doi:10.1002/cncr.35316

Impact of tocilizumab on anti-CD19 chimeric antigen receptor T-cell therapy in B-cell acute lymphoblastic leukemia

Cancer. 2024 Apr 5. doi: 10.1002/cncr.35316. Online ahead of print.

Authors

Xiangmin Wang^{1

2}, Bingpei Zhang^{1

2}, Qing Zhang^{1

2}, Hongyuan Zhou^{1

2}, Qian Sun^{1

2}, Yi Zhou^{1

2}, Tianci Li^{1

2}, Dian Zhou^{1

2}, Ziyuan Shen³, Jiaoli Zhang⁴, Ping Li⁵, Aibin Liang⁵, Keshu Zhou⁶, Lu Han⁶, Yongxian Hu⁷, Yun Yang⁸, Jiang Cao^{1

2}, Zhenyu Li^{1

2}, Kailin Xu^{1

2}, Wei Sang^{1

2}

Affiliations

¹ Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
² Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
⁴ Department of Rehabilitation, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁵ Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China.
⁶ Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
⁷ Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁸ Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

PMID: 38578977
DOI: 10.1002/cncr.35316

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.

Keywords: acute lymphoblastic leukemia; anti‐CD19; chimeric antigen receptor T cells; immune effector cell–associated neurotoxicity syndrome (ICANS); tocilizumab.

Abstract

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