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Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan

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Abstract

Background

Tisagenlecleucel, an autologous CD19-directed T-cell immunotherapy, can induce a durable response in adult patients with relapsed/refractory (r/r) B-cell lymphoma.

Methods

To elucidate the outcome of chimeric antigen receptor (CAR) T-cell therapy in Japanese, we retrospectively analyzed the outcomes of 89 patients who received tisagenlecleucel for r/r diffuse large B-cell lymphoma (n = 71) or transformed follicular lymphoma (n = 18).

Results

With a median follow-up of 6.6-months, 65 (73.0%) patients achieved a clinical response. The overall survival (OS) and event-free survival (EFS) rates at 12 months were 67.0% and 46.3%, respectively. Overall, 80 patients (89.9%) had cytokine release syndrome (CRS), and 6 patients (6.7%) had a grade ≥ 3 event. ICANS occurred in 5 patients (5.6%); only 1 patient had grade 4 ICANS. Representative infectious events of any grade were cytomegalovirus viremia, bacteremia and sepsis. The most common other adverse events were ALT elevation, AST elevation, diarrhea, edema, and creatinine elevation. No treatment-related mortality was observed. A Sub-analysis showed that a high metabolic tumor volume (MTV; ≥ 80 ml) and stable disease /progressive disease before tisagenlecleucel infusion were both significantly associated with a poor EFS and OS in a multivariate analysis (P < 0.05). Notably, the combination of these 2 factors efficiently stratified the prognosis of these patients (HR 6.87 [95% CI 2.4–19.65; P < 0.05] into a high-risk group).

Conclusion

We report the first real-world data on tisagenlecleucel for r/r B-cell lymphoma in Japan. Tisagenlecleucel is feasible and effective, even in late line treatment. In addition, our results support a new algorithm for predicting the outcomes of tisagenlecleucel.

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Acknowledgements

We thank all of the patients and their families who participated in this study. We are also grateful to Fumina Kusaka for her help in our research. We thank Japan Medical Communication for providing editorial assistance for this manuscript.

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Authors and Affiliations

  1. Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan

    Hideki Goto & Takanori Teshima

  2. Department of Hematology and Oncology, Kyoto University Hospital, Kyoto, Japan

    Toshio Kitawaki & Kazunori Toratani

  3. Division of Transfusion, Okayama University Hospital, Okayama, Japan

    Nobuharu Fujii

  4. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Koji Kato, Takuji Yamauchi & Masatoshi Shimo

  5. Department of Hematology, Tohoku University Hospital, Sendai, Japan

    Yasushi Onishi, Noriko Fukuhara & Koichi Onodera

  6. Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Hiroki Kobayashi

  7. Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Shota Yoshida, Hajime Senjo, Masahiro Onozawa & Takanori Teshima

  8. Department of Diagnostic Imaging, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Kenji Hirata

  9. Department of Biostatistics, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Isao Yokota

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  1. Hideki Goto
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  2. Toshio Kitawaki
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  3. Nobuharu Fujii
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  4. Koji Kato
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  9. Hiroki Kobayashi
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Contributions

H.G., T.K., N.F., K.K., Y.O., N.F., T.Y. and T.T. designed the study; H.G., T.K., N.F., K.K., Y.O., N.F., T.Y., K.T., H.K., S.Y., M.O., M.S., and K.O. provided assembled data; H.G., T.K., N.F., K.K., Y.O., N.F., T.Y., K.T., H.K., S.Y., M.S., and K.O. enrolled and treated patients; H.G., H.S., I.Y., and K.H. analyzed and interpreted the data; All authors participated in writing the manuscript, and provided feedback throughout the development process.

Corresponding author

Correspondence to Hideki Goto.

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Conflict of interest

H.G. has received honoraria from Bristol-Myers Squibb, Eisai, Janssen, Chugai, Novartis, SymBio, Kyowa-Kirin, Astellas, MSD and Daiichi-Sankyo; and has received research grants from Bristol-Myers Squibb and Kyowa-Kirin; and has received research funding from Kyowa-Kirin, AbbVie and Chugai. T.K. has received honoraria from Novartis, Otsuka, Bristol-Myers Squibb, Chugai, SymBio and Asahi Kasei. N.F. has received honoraria from Novartis, Chugai, Daiichi-Sankyo, Nippon Shinyaku, Janssen, Pfizer and Astellas. K.K. has received honoraria from Novartis, Chugai and Kyowa-Kirin; and has received research funding from Chugai, Takeda, Kyowa-Kirin, AbbVie, Novartis, Eisai, Janssen, Bristol-Myers Squibb, Ono and Daiichi-Sankyo. Y.O. has received honoraria from Novartis, Pfizer, Janssen, AbbVie, Chugai, Bristol-Myers Squibb, Amgen, Kyowa-Kirin, SymBio, Astellas, MSD, Meiji Seika; and has received research funding from Novartis, Pfizer, Janssen and Takara Bio. N.F. has received honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai, CLS Behring, Dainippon Sumitomo, Eisai, Janssen, Kyowa-Kirin, Nippon Shinyaku, Novartis, Ono, Otsuka, Sanofi, SymBio, Takeda and Zenyaku; and has received research funding from Bayer, Chugai, Celgene, Genmab and Incyte. K.O. has received honoraria from Novartis, AbbVie, Astellas, Janssen and Nippon Shinyaku; and has received research funding from Bristol-Myers Squibb, Celgene and Agois. T.Y., K.T., H.K., S.Y., M.S., H.S. M.O. and K.H. declare no competing interests. I.Y. has received grants from KAKENHI, AMED and Health, Labor and Welfare Policy Research Grants; and has received research funding from Nippon Medi-Physis; and has received honoraria from Chugai, Astra Zeneca and Nippon-Shinyaku. T.T. has received honoraria from Merck Sharp and Dohme, Takeda, Kyowa-Kirin, Bristol-Myers Squibb and Pfizer; and has received research funding from Chugai, Kyowa-Kirin, Sanofi, Astellas, TEIJIN PHARMA, Novartis, Fuji Pharma and Nippon Shinyaku; and served on an advisory board for Takeda and Novartis; and has participated in manuscript preparation as other financial interests for Janssen and Novartis.

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Goto, H., Kitawaki, T., Fujii, N. et al. Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan. Int J Clin Oncol 28, 816–826 (2023). https://doi.org/10.1007/s10147-023-02334-w

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