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Bendamustine versus chlorambucil in treatment of chronic lymphocytic leukaemia in China: a randomized, open-label, parallel-controlled, phase III clinical trial

  • Phase III Studies
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Summary

Background. Chronic lymphoblastic leukemia (CLL) is the most common adult leukemia and mainly affects the elderly. Chemoimmunotherapy still has a role in the standard frontline therapy for specific population. However, the clinical activity of bendamustine has not been investigated in unfit Chinese patients with CLL. This study aimed to compare the efficacy and safety of bendamustine versus chlorambucil for untreated Chinese patients with Binet stage B/C CLL. Methods. In this multi-center, randomized, open-label, parallel-controlled, phase III trial, patients with previously untreated CLL were enrolled and randomly assigned (1:1) to receive bendamustine or chlorambucil. The primary endpoint was the objective response rate. Secondary endpoints included progression-free survival, the duration of response, and overall survival. Adverse events were recorded to evaluate safety. Results. Of 158 screened patients, 147 were enrolled and randomly allocated to receive bendamustine (n = 72) or chlorambucil (n = 75). After a median follow-up of 25.6 months (IQR 12.5–27.7), 69.0% (95% CI, 56.9–79.5) of bendamustine-treated patients achieved objective response and 37.0% (95% CI, 26.0–49.1) of chlorambucil with a difference of 32.0% (95%CI: 16.6–47.5), demonstrating the superiority of bendamustine to chlorambucil (p < 0.001). The median progression-free survival was longer for bendamustine (16.5 months; 95% CI, 11.3–24.7) versus chlorambucil (9.6 months; 95% CI, 8.7–11.8; p < 0.001). A longer median duration of response was seen in those receiving bendamustine (19.2 months; 95% CI, 11.8–29.1) than chlorambucil (10.7 months; 95% CI, 5.6–13.6; p = 0.0018). Median overall survival was not reached in either group. Overall survival at 18 months was 88% for bendamustine versus 85% for chlorambucil. Most common adverse events in both groups were neutropenia and thrombocytopenia. Conclusion. In untreated Chinese patients with Binet stage B/C CLL, bendamustine induced the better objective response and resulted in longer progression-free survival than chlorambucil. Overall, these results validate the role of bendamustine as an effective and safe first-line therapy in this population.

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Data availability

The datasets generated for this study are available on request to the corresponding author.

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Author notes

  1. Daobin Zhou and Wei Xu these authors contributed equally to the manuscript and thus share the first authorship.

Authors and Affiliations

  1. Department of Hematology, Peking Union Medical College Hospital, Beijing, China

    Daobin Zhou

  2. Department of Hematology, Jiangsu Province Hospital, Jiangsu, China

    Wei Xu

  3. Department of Hematology, West China School of Medicine West China Hospital of Sichuan University, Sichuan, China

    Hongbing Ma

  4. Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, China

    Chunting Zhao

  5. Department of Hematology, Union Hospital Affiliated To Tongji Medical College of Huazhong University, Huazhong, China

    Yu Hu

  6. Department of Hematology, Hematology Hospital of Chinese Academy of Medical Sciences, Beijing, China

    Yaozhong Zhao

  7. Department of Hematology, The First Affiliated Hospital Of Soochow University, Soochow, China

    Depei Wu

  8. Department of Hematology, Xiangya Hospital Centeal South University, Xiangya, China

    Xielan Zhao & Yanjuan He

  9. Department of Hematology, The Second Hospital of Dalian Medical University, Dalian, China

    Jinsong Yan

  10. Department of Hematology, Sichuan Academy of Medical Sciences, Sichuan Provincial Peoples’s Hospital , Sichuan, China

    Chunsen Wang

  11. Department of Hematology, Dongguan Kanghua Hospital, Dongguan, China

    Fanyi Meng

  12. Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China

    Jie Jin

  13. Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China

    Xiaohong Zhang

  14. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Kang Yu

  15. Department of Hematology, Union Hospital Affiliated to Fujian Medical University, Fujian, China

    Jianda Hu

  16. Department of Hematology, Sun Yat-Sen University Cancer Center, Sun Yat-sen, China

    Yue Lv

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  1. Daobin Zhou
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  2. Wei Xu
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  3. Hongbing Ma
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Contributions

DZ and WX conceptualized and designed the study. HM and CZ constructed the forms to be filled with patient data. DZ, WX, YH, YZ and DW performed the data extraction from multiple centers. XZ, YH, JY, CW, FM, JJ, XZ, KY, JH, and YL recruited samples and collected clinicalpathologic data from their respective centers. DZ and WX drafted the manuscript. All authors reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Daobin Zhou.

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The studies involving human participants were reviewed and approved by an institutional review board (Approval number: 2008[27] and 2008[71]-2). Written informed consent for participation was obtained from each patient.

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Informed consent was obtained from all individual participants included in the study.

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Zhou, D., Xu, W., Ma, H. et al. Bendamustine versus chlorambucil in treatment of chronic lymphocytic leukaemia in China: a randomized, open-label, parallel-controlled, phase III clinical trial. Invest New Drugs 40, 349–360 (2022). https://doi.org/10.1007/s10637-021-01206-2

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