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Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study

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Abstract

This study aimed to identify the maximum-tolerated dose (MTD) of cyclophosphamide when combined with bortezomib and fludarabine (B-FC) in a phase 1b trial, and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL (rrMCL). Forty patients were enrolled between April 8, 2011, and October 10, 2015. The MTD of cyclophosphamide was identified to be 250 mg/m2 days 1–2. At a median follow-up of 31.6 months (13.5–47.4), among 32 patients in phase 2, 10 (31%) had a complete response and 13 (41%) had a partial response. The median progression-free survival was 21 months (95% CI 7.3–34.7), and the median overall survival was 32.4 months (95% CI 17.8–47.0). Grade 3–4 hematologic AEs included neutropenia (27%) and thrombocytopenia (39%). The B-FC regimen has satisfactory responses and manageable toxicities in rrMCL patients (ClinicalTrials.gov NCT01322776).

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The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval RDD number as RDDA2019001348.

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Acknowledgements

We appreciate the works by the Lym-4003 study collaborators.

Funding

This study was financially supported by the Xian-Janssen pharmaceuticals company.

Author information

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

    Xiao-Xiao Wang, Yan Gao, Qing-Qing Cai, Zhi-Ming Li, Wen-Qi Jiang & Hui-Qiang Huang

  2. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China

    Xiao-Xiao Wang, Yan Gao, Qing-Qing Cai, Zhi-Ming Li, Wen-Qi Jiang & Hui-Qiang Huang

  3. Department of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China

    Jie Jin

  4. Department of Medical Oncology, Fudan University Cancer Center, Shanghai, China

    Jun-Ning Cao

  5. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, China

    Ji-Feng Feng

  6. Department of Medical Oncology, People’s Hospital of Tianjin, Tianjin, China

    Hua-Qing Wang

  7. Department of Medical Oncology, Tianjin Cancer Hospital, Tianjin, China

    Hui-Lai Zhang

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  1. Xiao-Xiao Wang
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Consortia

on behalf of the Lymphoma Committee, Chinese Anti-Cancer Association (CACA)

Contributions

XXW and HQH designed the study. HQH, XXW, YG, JJ, JNC, JFF, HLZ, QQC, ZML, and WQJ recruited and cared for patients. XXW and YG contributed to data collection and data assembly. XXW, YG, and HQH did the data analyses and wrote the paper. All the authors contributed to interpretation of the data, critically revised the manuscript throughout development for intellectual content, approved the final version, and are responsible for the accuracy and integrity of the work.

Corresponding author

Correspondence to Hui-Qiang Huang.

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Xiao-Xiao Wang and Yan Gao are co-first authors.

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Wang, XX., Gao, Y., Jin, J. et al. Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study. Ann Hematol 100, 2961–2968 (2021). https://doi.org/10.1007/s00277-021-04619-4

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  • DOI: https://doi.org/10.1007/s00277-021-04619-4

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