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Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy

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Abstract

Chimeric antigen receptor T (CAR-T) cell therapy exhibits remarkable efficacy against refractory or relapsed multiple myeloma (RRMM); however, the immune deficiency following CAR-Ts infusion has not been well studied. In this study, 126 patients who achieved remission post-CAR-Ts infusion were evaluated for cellular immunity. Following lymphodepletion (LD) chemotherapy, the absolute lymphocyte count (ALC) and absolute counts of lymphocyte subsets were significantly lower than baseline at D0. Grade ≥ 3 lymphopenia occurred in 99% of patients within the first 30 days, with most being resolved by 180 days. The median CD4+ T-cell count was consistently below baseline and the lower limit of normal (LLN) levels at follow-up. Conversely, the median CD8+ T-cell count returned to the baseline and LLN levels by D30. The median B-cell count remained lower than baseline level at D60 and returned to baseline and LLN levels at D180. In the first 30 days, 27 (21.4%) patients had 29 infections, with the majority being mild to moderate in severity (21/29; 72.4%). After day 30, 44 (34.9%) patients had 56 infections, including 20 severe infections. One patient died from bacteremia at 3.8 months post-CAR-Ts infusion. In conclusion, most patients with RRMM experienced cellular immune deficiency caused by LD chemotherapy and CAR-Ts infusion. The ALC and most lymphocyte subsets gradually recovered after day 30 of CAR-Ts infusion, except for CD4+ T cells. Some patients experience prolonged CD4+ T-cell immunosuppression without severe infection.

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The data presented in this study are available in this article (and Supplementary Materials).

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Funding

This work was financially supported by Grants from the Key Research & Development Plan of Jiangsu Province (BE2018634, BE2020681, BE2022711), Xuzhou Medical leading talents Training Program (XWRCHT20210028).

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Author notes

  1. Hai Cheng, Shengwei Ji, Jiaojiao Wang and Tian Hua have contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China

    Hai Cheng, Shengwei Ji, Jiaojiao Wang, Tian Hua, Zihan Chen, Jiaying Liu, Lingyan Shao, Xue Wang, Wei Chen, Wei Sang, Kunming Qi, Zhenyu Li, Cai Sun, Kailin Xu & Jiang Cao

  2. Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, China

    Ming Shi & Junnian Zheng

  3. Jiangsu Bone Marrow Stem Cell Institute, Xuzhou, 221002, China

    Jianlin Qiao, Qingyun Wu & Lingyu Zeng

  4. Department of Hematology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, China

    Xiaoming Fei

  5. Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, 226000, China

    Hongming Huang

  6. Department of Hematology, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China

    Weiying Gu

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  1. Hai Cheng
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Contributions

HC and JC designed and supervised the study; XW, WC, WS, KQ, ZL, CS, FX, HH and WG and their respective research teams recruited and followed up with the patients and provided clinical data; SJ, JW, TH, ZC, JL and LS collected and analyzed the research data; HC, SJ, JW, TH and JC performed statistical analyses; SJ, JW, TH, ZC, JL, LS, XW, WS and KQ took care of the patients and evaluated responses; HC, SJ and JC drafted and revised the manuscript; MS, JQ, QW and LZ contributed to laboratory monitoring of the patients; KX, JZ and JC provided support for the project. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kailin Xu, Junnian Zheng or Jiang Cao.

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Conflicts of interest

The authors declare that they have no conflict of interests.

Ethics approval

The study was approved by the Ethics Committees of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China (REC ref no. XYFY2020-KL062, XYFY2019-KL182, XYFY2017-KL013).

Consent to participate

All patients provided written informed consent. This study was registered on Chictr.org.cn, number ChiCTR2000033567, ChiCTR-OIC-17011272, ChiCTR1900026219.

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Cheng, H., Ji, S., Wang, J. et al. Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy. Clin Exp Med 23, 5241–5254 (2023). https://doi.org/10.1007/s10238-023-01232-9

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