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Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant

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Abstract   

The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 regimen, especially when antiplatelet agents were co-prescribed, was also evaluated. We retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed (R/R) patients with DLBCL who were administered with ZR2 regimen in two medical centers between December 2019 and February 2022. Response rates, progression-free survival (PFS), overall survival (OS), bleeding adverse events (AEs), and thrombosis episodes were analyzed. Furthermore, we investigated the effects of zanubrutinib alone or in combination with lenalidomide on platelet functions in vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL patients) who received ZR2 regimen were enrolled in the study (median age: 69.5 years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 50.1%, respectively. The median follow-up was 16.6 months. The median PFS and OS were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred in four cases, three cases suffered severe bleeding events, and thrombosis events were observed in two patients. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 is an efficient treatment option for unfit patients with DLBCL and could be well tolerated. Notably, this regimen inhibited platelet functions. Antiplatelet agents should be used with caution in patients treated with this regimen.

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Funding

This work was supported by National Science Foundation of China under Grant (82100215), Science Foundation of Shanghai under Grant (22ZR1411400), Youth Foundation of the Affiliated Hospital of Qingdao University (QDFYQN 202101009), Cancer Research Foundation of Huiyu Pharmaceutical (GH000027).

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Author notes

  1. Yawen Wang, Jiadai Xu, and Panpan Li contributed equally to this study.

Authors and Affiliations

  1. Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China

    Yawen Wang, Jiadai Xu, Panpan Li & Peng Liu

  2. Department of Hematology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China

    Yawen Wang & Hongwei Xue

  3. Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China

    Jiadai Xu, Panpan Li & Peng Liu

  4. Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yanyan Xu

Authors
  1. Yawen Wang
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  2. Jiadai Xu
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  3. Panpan Li
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  4. Yanyan Xu
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  5. Hongwei Xue
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  6. Peng Liu
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Contributions

Conception and design: Peng Liu, Hongwei Xue, Jiadai Xu. Management of patients: Jiadai Xu, Hongwei Xue. Data collection: Yawen Wang, Panpan Li. Experiment conduction: Panpan Li, Yawen Wang. Data analysis and manuscript writing: Yawen Wang. Manuscript revising: Jiadai Xu, Peng Liu.

Corresponding authors

Correspondence to Hongwei Xue or Peng Liu.

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Ethical approval and consent to participate

This study was approved by the ethics committee of Zhongshan Hospital Fudan University (approval number B2023-184) and was in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all patients.

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The authors declare no competing interests.

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Wang, Y., Xu, J., Li, P. et al. Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant. Ann Hematol 103, 499–510 (2024). https://doi.org/10.1007/s00277-023-05498-7

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  • DOI: https://doi.org/10.1007/s00277-023-05498-7

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