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Evaluation of Bruton tyrosine kinase inhibitors monotherapy and combination therapy in lymphocytic leukemia

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A Correction to this article was published on 02 December 2023

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Abstract

BTKi is an effective treatment in chronic lymphocytic leukemia. However, head-to-head clinical trials between BTKi are rare. To explore evidence-based treatment decisions, we conducted this network meta-analysis. We searched in PubMed, Cochrane Library and Embase and selected articles of BTKi treatment in CLL patients, with English restrictions. Objective response rate (ORR), progression-free survival (PFS) and safety were outcomes. Combination therapy and acalabrutinib monotherapy achieved great ORR (greater than 80%). Combination therapy (AO and IR) also performed terrific PFS (> 80%). Compared with ibrutinib monotherapy, zanubrutinib, acalabrutinib and IR showed no significance in overall survival. Diarrhea, hypertension, cardiac events, neutropenia were common adverse events of BTKi therapy. IR had higher incidence of hypertension (0.38, 95% CI 0.28–0.48), and IU was more likely occurred cardiac events. Zanubrutinib monotherapy had lower incidence of total serious adverse reaction (0.42, 95% confidence interval (95% CI): 0.36–0.47),while ibrutinib monotherapy occurred higher adverse reactions of grade ≥ 3 (0.77, 95% CI 0.72–0.82). Although both BTKi monotherapy and combination therapy showed great efficacy, combination therapy did not display priority. Meanwhile, safety of BTKi combination therapy needs to be fully and comprehensively considered.

Registration number: CRD42022378732.

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Data availability

All data could be obtained from corresponding author.

Change history

Abbreviations

AO:

Acalabrutinib plus Obinutuzumab

IU:

Ibrutinib plus Ublituximab

IR:

Ibrutinib plus Rituximab

Aca:

Acalabrutinib

Ibr:

Ibrutinib

Zan:

Zanubrutinib

PFS:

Progression-free survival

CLL:

Chronic lymphocytic leukemia

SLL:

Small lymphocytic lymphoma

BTKi:

Bruton’s tyrosine kinase inhibitors

ORR:

Objective response rate

PFS:

Progression-free survival

OS:

Overall survival

AEs:

Adverse events

TEAEs:

Treatment-emergent adverse events

SAE:

Serious adverse events

NMA:

Network meta-analysis

iwCLL:

International Workshop on CLL

RCTs:

Randomized controlled trials

ECOG:

Eastern Cooperative Oncology Group

95%CI:

95% confidence interval

SUCRA:

Surface Under Cumulative Ranking

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

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Acknowledgements

Yi Fang, Jin Lu and Qian Lu contributed to study design and guidance support. Liming Chen and Nan Peng selected eligible studies. Binyi Hu, Dingyuan Hu and Jiaojiao Zhang extracted and analyzed the data from original articles. Lijue Wang and Zhenwei Xie made the charts and interpreted the results. Suping Niu and Xiangxing Liu interpreted the results and wrote the manuscript. Xiangxing Liu contributed to review and revised the manuscript. All authors read and approved the final version of the manuscript. Thanks to all the authors for the efforts of this study.

Funding

This study was funded by the project “Demonstration construction project of research ward (4102000007).”

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Author notes

  1. Nan Peng and Liming Chen are the two co-first authors to this article.

Authors and Affiliations

  1. Department of Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, China

    Xiangxing Liu, Binyi Hu & Jiaojiao Zhang

  2. Clinical Trial Institution, Peking University People’s Hospital, 100044, Beijing, China

    Xiangxing Liu, Binyi Hu, Dingyuan Hu, Jiaojiao Zhang, Lijue Wang, Zhenwei Xie & Yi Fang

  3. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, 100044, Beijing, China

    Nan Peng & Jin Lu

  4. Nursing Department, Peking University People’s Hospital, 100044, Beijing, China

    Liming Chen

  5. Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, 100044, Beijing, China

    Dingyuan Hu

  6. Clinical Trial Institution, Scientific Research Department, Peking University People’s Hospital, 100044, Beijing, China

    Suping Niu

  7. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, China

    Qian Lu

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Contributions

Yi Fang, Jin Lu and Qian Lu contributed to study design and guidance support. Liming Chen and Nan Peng selected eligible studies. Binyi Hu, Dingyuan Hu and Jiaojiao Zhang extracted and analyzed the data from original articles. Lijue Wang and Zhenwei Xie made the charts and interpreted the results. Suping Niu and Xiangxing Liu interpreted the results and wrote the manuscript. Xiangxing Liu contributed to review and revised the manuscript. All authors read and approved the final version of the manuscript. Thanks to all the authors for the efforts of this study.

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Correspondence to Jin Lu or Yi Fang.

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We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors have no relevant financial or non-financial interests to disclose.

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Liu, X., Hu, B., Peng, N. et al. Evaluation of Bruton tyrosine kinase inhibitors monotherapy and combination therapy in lymphocytic leukemia. Clin Exp Med 23, 4237–4248 (2023). https://doi.org/10.1007/s10238-023-01208-9

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