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Cytokine profiles are associated with prolonged hematologic toxicities after B-cell maturation antigen targeted chimeric antigen receptor–T-cell therapy

  • Linqin Wang
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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  • Ruimin Hong
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
    Search for articles by this author
  • Linghui Zhou
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
    Search for articles by this author
  • Yiyun Wang
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
    Search for articles by this author
  • Yuqi Lv
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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  • Fang Ni
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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  • Mingming Zhang
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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  • Houli Zhao
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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  • Shuyi Ding
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;
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  • Alex H. Chang
    Affiliations
    Shanghai YaKe Biotechnology Ltd.

    Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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  • Huijun Xu
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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  • Yongxian Hu
    Correspondence
    Correspondence: Yongxian Hu, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University. No.79 Qingchun Road, Hangzhou, China.
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
    Search for articles by this author
  • Guoqing Wei
    Correspondence
    Correspondence: Guoqing Wei, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University. No.79 Qingchun Road, Hangzhou, China.
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
    Search for articles by this author
  • He Huang
    Correspondence
    Correspondence: He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University. No.79 Qingchun Road, Hangzhou, China.
    Affiliations
    Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

    Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;

    Institute of Hematology, Zhejiang University, Hangzhou, China;

    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
    Search for articles by this author
Published:December 07, 2022DOI:https://doi.org/10.1016/j.jcyt.2022.11.001

      Abstract

      Background aims

      The considerable efficacy of B-cell maturation antigen–targeted chimeric antigen receptor (CAR)–T-cell therapy has been extensively demonstrated in the treatment of relapsed or refractory multiple myeloma. Nevertheless, in clinical practice, prolonged hematologic toxicity (PHT) extends hospital stay and impairs long-term survival.

      Methods

      This retrospective study reviewed 99 patients with relapsed or refractory multiple myeloma who underwent B-cell maturation antigen CAR–T-cell therapy at our institution between April 2018 and September 2021 (ChiCTR1800017404).

      Results

      Among 93 evaluable patients, the incidence of prolonged hematologic toxicities was high after CAR–T-cell infusion, including 38.71% (36/93) of patients with prolonged neutropenia, 22.58% (21/93) with prolonged anemia and 59.14% (55/93) with prolonged thrombocytopenia. In addition, 9.68% (9/93) of patients experienced prolonged pancytopenia. Our multivariate analyses identified that cytokine profiles were independent risk factors for PHTs, whereas a sufficient baseline hematopoietic function and high CD4/CD8 ratio of CAR-T cells were protective factors for PHTs after CAR–T-cell infusion. Subgroup analyses found that the kinetics of post-CAR-T hematologic parameters were primarily determined by the collective effects of cytokine release syndrome and baseline hematopoietic functions, and showed influential weights for the three lineages.

      Conclusions

      Our findings improve the understanding of the impact of cytokines on hematopoietic functions, which could contribute to the mechanism investigation and exploration of potential intervention strategies.

      Key Words

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