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Predictive value of next-generation sequencing-based minimal residual disease after CAR-T cell therapy

Bone Marrow Transplantation volume 57, pages 1350–1353 (2022)Cite this article

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Minimal residual disease (MRD) is closely associated with risk stratification of hematological malignancies [1]. Chimeric antigen receptor T (CAR-T) cell therapy, specifically redirects genetically modified immune cells to fight against hematologic malignancies. Studies have demonstrated that nearly 80–90% of patients with acute lymphoblastic leukemia (ALL) achieve complete remission (CR) after CAR-T cell therapy [2, 3]; however, the 1-year relapse rate is still as high as 50–60% [4, 5]. Given the situation, next-generation sequencing (NGS)—MRD can accurately and quantitatively monitor patient-specific tumor cells (up to 10E−6) to reveal accurate and highly sensitive MRD levels [6, 7]. In this retrospective study, we estimated the sensitivity and concordance of NGS-MRD and FC-MRD of 20 patients with relapsed/refractory B-ALL who achieved CR after CAR-T cell therapy and further demonstrated the prognostic value of post-CART NGS-MRD at day 30 for ALL patients receiving CAR-T cell therapy.

We retrospectively identified at least one trackable IG clonal sequence in the pre-CAR-T BM specimens from 20 patients with relapsed/refractory B-cell ALL who achieved CR (MRD < 0.01% evaluated by FC) at the first follow-up (Fig. S1).The leukemic clonal sequence was a complete IGH-VDJ rearrangement in 18 patients (90%), IGK rearrangement in four patients (20%), and IGL rearrangement in four patients (20%). We measured the MRD in 63 samples (Table S1). Using a threshold of 0.01% (1 in 10,000), the determination of the presence (or absence) of leukemia was concordant in 46/63 (73%) of the samples. Discordance between NGS and FC was identified in 17/63 samples (27%).

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Fig. 1: MRD detection and clinical outcomes of patients treated with CAR-T cells.

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All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).

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Acknowledgements

This work was supported by the 973 Program (Project No. 2015-CB964900), the Natural Science Foundation of China (Project No. 81770201 and No. 81730008). This trial was registered at www.chictr.org.cn as # ChiCTR1800018468 and # ChiCTR-OCC-15007008.

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Author notes

  1. These authors contributed equally: Yue Huang, Houli Zhao, Mi Shao

Authors and Affiliations

  1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yue Huang, Houli Zhao, Mi Shao, Linghui Zhou, Xiaoqing Li, Guoqing Wei, Wenjun Wu, Jiazhen Cui, Yongxian Hu & He Huang

  2. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China

    Yue Huang, Houli Zhao, Mi Shao, Linghui Zhou, Xiaoqing Li, Guoqing Wei, Wenjun Wu, Jiazhen Cui, Yongxian Hu & He Huang

  3. Institute of Hematology, Zhejiang University, Hangzhou, China

    Yue Huang, Houli Zhao, Mi Shao, Linghui Zhou, Xiaoqing Li, Guoqing Wei, Wenjun Wu, Jiazhen Cui, Yongxian Hu & He Huang

  4. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China

    Yue Huang, Houli Zhao, Mi Shao, Linghui Zhou, Xiaoqing Li, Guoqing Wei, Wenjun Wu, Jiazhen Cui, Yongxian Hu & He Huang

  5. Shanghai YaKe Biotechnology Ltd, Shanghai, China

    Alex H. Chang

  6. Hangzhou ImmuQuad Biotech, LLC., Hangzhou, China

    Tao Sun

  7. Institute of Wenzhou, Zhejiang University, Wenzhou, China

    Tao Sun

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Contributions

YH, HZ and MS collected the patients’ data and drafted the manuscript. TS, YXH and HH conceived and designed the study. YXH revised the manuscript along with GW, WW and AHC and these individuals were responsible for the treatment of these patients. All authors checked and approved the final manuscript.

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Correspondence to Tao Sun, Yongxian Hu or He Huang.

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Huang, Y., Zhao, H., Shao, M. et al. Predictive value of next-generation sequencing-based minimal residual disease after CAR-T cell therapy. Bone Marrow Transplant 57, 1350–1353 (2022). https://doi.org/10.1038/s41409-022-01699-2

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