Chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma: opportunities and challenges

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B-cell non-Hodgkin lymphoma (NHL) is the most frequent hematologic malignancy. Despite the refinement of chemoimmunotherapy, a substantial number of patients experience chemorefractory disease. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is considered the most promising and effective therapy to overcome chemorefractory B-cell NHL. Based on the promising results obtained from pivotal trials, the US Food and Drug Administration and European Medicines Agency approved anti-CD19 CAR T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma. Nonetheless, there remain several controversial issues and problems awaiting solutions, including optimal management of toxicities, overcoming relapsed/refractory disease after CAR T-cell therapy, and improving CAR-T manufacturing platform. Definite unmet medical needs among patients with chemorefractory B-cell NHL still exist. CAR T-cell therapy might be a game changer that can defeat chemorefractory B-cell NHL, and further clinical development is warranted. In this review, we summarize the recent clinical developments, clinical implications, and perspectives of CAR T-cell therapy, focusing on B-cell NHL.

Keywords: axicabtagene ciloleucel, B-cell non-Hodgkin lymphoma, CAR-T, CD19, chimeric antigen receptor, diffuse large B-cell lymphoma, lisocabtagene maraleucel, tisagenlecleucel.

Citation: Makita S, Imaizumi K, Kurosawa S, Tobinai K. Chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma: opportunities and challenges. Drugs in Context 2019; 8: 212567. DOI: 10.7573/dic.212567

Contributions: SM wrote the initial draft of this manuscript. KI, SK, and KT assisted in the preparation of the manuscript. The final version of the manuscript was approved by all authors. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: SM, KI, and SK have nothing to disclose. KT received consulting fees and lecture fees from Zenyaku Kogyo, grant support and lecture fees from Eisai, Takeda, Mundipharma International, Janssen, Kyowa Hakko Kirin, Chugai Pharma, and Ono Pharmaceutical, grant support, consulting fees, and lecture fees from HUYA Bioscience International, and grant support from GlaxoSmithKline, Servier, and AbbVie. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at

Acknowledgments: We thank members of Team CAR-T at the National Cancer Center Hospital (NCCH) for supporting the CAR-T therapy: Ms Moemi Kasane, Ms Saori Nakabayashi (Cell Preparation Technicians), Mr Hidekazu Fukumoto (Medical engineer), Ms Yukari Torihata, Mr Katsuyuki Ikarashi, and Ms Hiroko Takagi (Clinical Research Coordinators). We also thank Dr Takahiro Fujino, Dr Yo Saito (Fellows), Dr Akiko Miyagi Maeshima (Pathologist), Dr Tetsufumi Sato (ICU doctor), and Dr Yasuji Miyakita (Neurologist) for their great cooperation to the CAR-T trials. Lastly we thank Dr Koji Izutsu, Chief of the Department of Hematology, NCCH.

Funding declaration: This work was supported in part by the National Cancer Center Research and Development Fund (26-A-4 and 27-A-2). Language editing was provided by Editage and was supported the internal fund of the National Cancer Center Hospital Tokyo, Japan.

Copyright: Copyright © 2019 Makita S, Imaizumi K, Kurosawa S, Tobinai K. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2019 Makita S, Imaizumi K, Kurosawa S, Tobinai K. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

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Correspondence: Shinichi Makita, Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Provenance: invited; externally peer reviewed.

Submitted: 22 October 2018; Peer review comments to author: 28 November 2018; Revised manuscript received: 15 January 2019; Accepted: 16 January 2019; Publication date: 13 February 2019.

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