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HBV reactivation in patients with chronic or resolved HBV infection following BCMA-targeted CAR-T cell therapy

Bone Marrow Transplantation volume 58, pages 701–709 (2023)Cite this article

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Abstract

B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). Concern of the safety and efficacy of CAR-T cell therapy in patients with chronic or resolved HBV infection is raised. In this study, we retrospectively reviewed 99 patients with r/r MM treated with BCMA-targeted CAR-T cell therapy, of which 7 (7.1%) patients had chronic HBV infection, 43 (43.4%) with resolved HBV infection, and the remaining 49 (49.49%) HBV-uninfected. Patients’ characteristics before CAR-T cell administration were comparable in different status of HBV infection. Patients’ liver function, cytokine levels, CAR-T cell expansion and cytokine release syndrome (CRS) grade after CAR-T cell therapy did not differ in different HBV serologic status. Furthermore, chronic HBV infection or resolved HBV infection did not affect clinical response, progress-free survival (PFS), or overall survival (OS). Four (4.04%) patients experienced HBV reactivation, 3 (6.98%) with resolved HBV infection, and 1 (14.29%) chronic HBV infection. Of 4 patients with HBV reactivation, 2 cases (50%) of severe hepatitis were noted and reported. Drops of serum IgG and elevation of alanine aminotransferase (ALT), alanine aminotransferase (AST), total bilirubin (TB) were observed in all four patients around the date of HBV reactivation.

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Fig. 1: Patients diagram.
Fig. 2: Liver function and cytokine levels in 30 days after BCMA-targeted CAR-T cell therapy in patients with different HBV serologic status.
Fig. 3: Blood cell counts and CAR-T cell expansion in 30 days after BCMA-targeted CAR-T cell therapy in patients with different HBV serologic status.
Fig. 4: Clinical outcomes in patients with different HBV serologic status.
Fig. 5: Serum immunoglobulin (Ig) levels, including IgA, IgG, IgM in four patients with HBV reactivation.
Fig. 6: Liver functions, including alanine aminotransferase (ALT), alanine aminotransferase (AST), total bilirubin (TB) in four patients with HBV reactivation.

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All data can be obtained from corresponding author for appropriate reason.

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Acknowledgements

This work was supported by Zhejiang Provincial Key Medical Discipline (Medical Tissue Engineering). We sincerely thank the patient and his family for their trust and all colleagues for their efforts from the Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University. We sincerely thank the support from the National Natural Science Foundation of China (81730008).

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Author notes

  1. These authors contributed equally: Shan Fu, Qiqi Zhang, Ruirui Jing, Cheng Zu.

Authors and Affiliations

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

    Shan Fu, Qiqi Zhang, Ruirui Jing, Cheng Zu, Fang Ni, Yuqi Lv, Jiazhen Cui, Haiqiong Zheng, Mingming Zhang, Guoqing Wei, Zenan Cen, Yongxian Hu & He Huang

  2. Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China

    Shan Fu, Qiqi Zhang, Ruirui Jing, Cheng Zu, Fang Ni, Yuqi Lv, Jiazhen Cui, Haiqiong Zheng, Mingming Zhang, Guoqing Wei, Zenan Cen, Yongxian Hu & He Huang

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

    Shan Fu, Qiqi Zhang, Ruirui Jing, Cheng Zu, Fang Ni, Yuqi Lv, Jiazhen Cui, Haiqiong Zheng, Mingming Zhang, Guoqing Wei, Zenan Cen, Yongxian Hu & He Huang

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

    Shan Fu, Qiqi Zhang, Ruirui Jing, Cheng Zu, Fang Ni, Yuqi Lv, Jiazhen Cui, Haiqiong Zheng, Mingming Zhang, Guoqing Wei, Zenan Cen, Yongxian Hu & He Huang

  5. Shanghai YaKe Biotechnology Ltd., Shanghai, China

    Yanlei Zhang & Alex H. Chang

  6. Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China

    Alex H. Chang

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  1. Shan Fu
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Contributions

FS, QZ, YH and HH designed the study; FS, QZ, ZC, RJ, FN, YL, HZ and JC analyzed and interpreted the data; QZ, CZ, YH, and HH drafted the article; ZC revised the article; AHC and YZ helped manufacture of CAR-T cells; YH, MZ, GW and HH provided CAR-T cell treatment and care to patients.

Corresponding authors

Correspondence to Yongxian Hu or He Huang.

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Competing interests

Author YZ and AHCis employed by Shanghai YaKe Biotechnology Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Fu, S., Zhang, Q., Jing, R. et al. HBV reactivation in patients with chronic or resolved HBV infection following BCMA-targeted CAR-T cell therapy. Bone Marrow Transplant 58, 701–709 (2023). https://doi.org/10.1038/s41409-023-01960-2

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