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FULL-LENGTH ARTICLE Clinical Research| Volume 25, ISSUE 6, P653-658, June 2023

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Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma

  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Sha Ma
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Hujun Li
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Dian Zhou
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Xiaotian Zhang
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Ming Shi
    Affiliations
    Cancer Institute, Xuzhou Medical University, Xuzhou, China

    Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Jiang Cao
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Yuekun Qi
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Jieyun Xia
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Yang Liu
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Xue Wang
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Depeng Li
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Wei Sang
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Zhiling Yan
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Feng Zhu
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Haiying Sun
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Hai Cheng
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Junnian Zheng
    Affiliations
    Cancer Institute, Xuzhou Medical University, Xuzhou, China

    Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Kailin Xu
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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  • Zhenyu Li
    Correspondence
    Correspondence: Zhenyu Li and Ying Wang, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Rd, Xuzhou, Jiangsu 221002, China.
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Kunming Qi
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Ying Wang
    Correspondence
    Correspondence: Zhenyu Li and Ying Wang, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Rd, Xuzhou, Jiangsu 221002, China.
    Affiliations
    Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
    Search for articles by this author
  • Author Footnotes
    ⁎ These authors contributed equally to this work.
Published:March 11, 2023DOI:https://doi.org/10.1016/j.jcyt.2023.01.011

      Abstract

      Background aims

      Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM). We present a retrospective study performed on 113 patients with R/R MM who received single anti-BCMA CAR T-cell, combined with anti-CD19 CAR T-cell or anti-CD138 CAR T-cell therapy.

      Methods

      Eight patients were given G-CSF after successful management of CRS, and no CRS re-occurred thereafter. Of the remaining 105 patients that were finally analyzed, 72 (68.6%) received G-CSF (G-CSF group), and 33 (31.4%) did not (non G-CSF group). We mainly analyzed the incidence and severity of CRS or NEs in two groups of patients, as well as the associations of G-CSF timing, cumulative dose and cumulative time with CRS, NEs and efficacy of CAR T-cell therapy.

      Results

      Both groups of patients had similar duration of grade 3–4 neutropenia, and the incidence and severity of CRS or NEs.There were also no differences in the incidence and severity of CRS or NEs between patients with the timing of G-CSF administration ≤3 days and those >3 days after CAR T-cell infusion. The incidence of CRS was greater in patients receiving cumulative doses of G-CSF >1500 μg or cumulative time of G-CSF administration >5 days. Among patients with CRS, there was no difference in the severity of CRS between patients who used G-CSF and those who did not. The duration of CRS in anti-BCMA and anti-CD19 CAR T-cell–treated patients was prolonged after G-CSF administration. There were no significant differences in the overall response rate at 1 and 3 months between the G-CSF group and the non–G-CSF group.

      Conclusions

      Our results showed that low-dose or short-time use of G-CSF was not associated with the incidence or severity of CRS or NEs, and G-CSF administration did not influence the antitumor activity of CAR T-cell therapy.

      Key Words

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