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Modified EASIX scores predict severe CRS/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy

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Abstract

Chimeric antigen receptor T (CAR-T) cell therapy targeting CLL1 has been considered a potent weapon for patients with acute myeloid leukemia (AML). This study aims to evaluate the efficacy and toxicity of CLL1 CAR-T cell therapy in a larger cohort, with particular attention to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Among the 32 patients assessed for efficacy, complete remission occurred in 71.88% (23/32) of cases and undetectable minimal residual disease in 14 patients. The CRS developed in all patients, with 8 individuals experiencing ICANS. Severe CRS and ICANS were observed in 11 and 2 patients, respectively. Furthermore, the Endothelial Activation and Stress Index (EASIX) and its derivatives measured before and after CLL1 CAR-T cell infusion were employed for predicting the severe complications. Significant differences were observed in EASIX scores on the day before lymphodepletion (Day BL, P = 0.023), −1 (P < 0.001), +1 (P < 0.001), and +3(P = 0.014); sEASIX scores on Day BL (P = 0.007), −1 (P < 0.001), +1 (P < 0.001), and +3 (P < 0.001); and mEASIX score on Day −1 (P = 0.004) between patients with mild and severe CRS/ICANS. Additionally, there was a significant difference in mEASIX scores between responders and non-responders on Day BL (P = 0.004) and Day −1 (P = 0.044). Our findings indicate that pre- and post-infusion assessments of EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS and treatment response following CLL1 CAR-T cell therapy, which can assist physicians in implementing preemptive treatment strategies for potential severe complications and screening patients who are suitable candidates for CLL1 CAR-T cell therapy. EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS following CLL1 CAR-T cell therapy. The preinfusion mEASIX scores of CLL1 CAR-T cells can effectively predict treatment response.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author at mingfengzhao@sina.com upon reasonable request.

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Acknowledgements

The authors thank the patients and their families for contributing to this study.

Funding

This work was supported by grants from the General Project of the National Natural Science Foundation of China (81970180 to MFZ), the Science and Technology Project of Tianjin Municipal Health Committee (TJWJ2022QN030 to MFZ), Key Projects of Tianjin Applied Basic Research and Multi-Investment Fund (21JCZDJC01240), Science and Technology Project of Tianjin Municipal Health Committee (TJWJ2022XK018 to MFZ), and the Key Science and Technology Support Project of Tianjin Science and Technology Bureau (20YFZCSY00800 to MFZ), as well as Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-056B).

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  1. YFZ, XMZ and MZ contributed equally as co-first authors.

Authors and Affiliations

  1. The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China

    Yifan Zhao, Meng Zhang, Ruiting Guo & Yi Zhang

  2. Nankai University School of Medicine, Tianjin, 300380, China

    Xiaomei Zhang

  3. Department of Hematology, Tianjin First Central Hospital, Tianjin, 300380, China

    Yedi Pu, Haibo Zhu, Pengjiang Liu, Yu Zhang, Xiaoyuan He, Cuicui Lyu, Hairong Lyu, Xia Xiao & Mingfeng Zhao

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  1. Yifan Zhao
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Contributions

Conceptualization of the project: YFZ, XMZ, MZ, XX, and MFZ.

Development of methodology: YFZ.

Manufacturing of CLL1 CAR-T products: XMZ and MZ.

Management of patients: RTG, YZ, YDP, HBZ, PJL, YZ, XYH, CCL, and HRL.

Collection, analysis, and interpretation of data: RTG, YZ, YDP, HBZ, PJL, YZ, XYH, CCL, and HRL.

Writing articles and revision of the manuscript: YFZ, XX, and MFZ.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Xia Xiao or Mingfeng Zhao.

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The study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin First Center Hospital.

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Zhao, Y., Zhang, X., Zhang, M. et al. Modified EASIX scores predict severe CRS/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy. Ann Hematol 103, 969–980 (2024). https://doi.org/10.1007/s00277-024-05617-y

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