Alpha 2.0
Login Register
» Articles » PMID: 39441428

Treatment-free Remission After Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia in the Chronic Phase: a Systematic Review and Meta-analysis

Overview
Journal Discov Oncol
Publisher Springer
Specialty Oncology
Date 2024 Oct 23
PMID 39441428
Authors
Zhenxiang Zheng
Hao Tang
Xinxia Zhang
Liling Zheng
Zhao Yin
Jie Zhou
Yangmin Zhu
Affiliations
Soon will be listed here.
Abstract

Background: Treatment-free remission (TFR) is a new long-term goal for treating selected patients with chronic myeloid leukemia in the chronic phase (CML-CP). Still, the appropriate group in which TFR can be attempted and the factors influencing it have not yet been identified. This meta-analysis aimed to explore TFR in CML-CP patients who achieved a deep molecular response (DMR) before Tyrosine kinase inhibitors (TKIs) discontinuation and to explore possible factors influencing TFR and the safety of discontinuation.

Methods: We performed a systematic review and single-arm meta-analysis with a systematic search of published literature up to September 2023 in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. The assessment was performed using the MINORS scale. Random-effects models were used to calculate outcome metrics, including overall mean TFR rates at 12 and 24 months and subgroup differences. Data synthesis and analysis were done by Stata17.0 software.

Results: A total of 19 single-arm trials involving 2336 patients were included in this meta-analysis, with an overall mean TFR rate of 59% [95CI:0.56-0.63] at 12 months and 55% [95CI:0.52-0.59] at 24 months, and no CML-related deteriorations or deaths reported during the TFR period. Our subgroup analysis showed that better TFR was associated with prior interferon therapy (P = 0.003), and molecular response depth MR5.0 (P = 0.020).

Conclusion: Our study demonstrated that prior interferon therapy and attainment of a molecular response depth of MR5.0 or greater were associated with higher TFR rates, with patients who attained MR5.0 or greater achieving a TFR rate of up to 62% in the second year after TKI discontinuation. Considering the high heterogeneity of the included trials, the above influences still require further validation and more detailed subgroup analysis in future discontinuation trials.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ (Registration No. CRD42023471334).

References
1.
Rea D, Nicolini F, Tulliez M, Guilhot F, Guilhot J, Guerci-Bresler A . Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2016; 129(7):846-854. DOI: 10.1182/blood-2016-09-742205. View
2.
Hochhaus A, Baccarani M, Silver R, Schiffer C, Apperley J, Cervantes F . European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020; 34(4):966-984. PMC: 7214240. DOI: 10.1038/s41375-020-0776-2. View
3.
Shanmuganathan N, Pagani I, Ross D, Park S, Yong A, Braley J . Early BCR-ABL1 kinetics are predictive of subsequent achievement of treatment-free remission in chronic myeloid leukemia. Blood. 2020; 137(9):1196-1207. DOI: 10.1182/blood.2020005514. View
4.
Yoshida C, Yamaguchi H, Doki N, Murai K, Iino M, Hatta Y . Importance of TKI treatment duration in treatment-free remission of chronic myeloid leukemia: results of the D-FREE study. Int J Hematol. 2023; 117(5):694-705. PMC: 10121524. DOI: 10.1007/s12185-023-03549-3. View
5.
Kimura S, Imagawa J, Murai K, Hino M, Kitawaki T, Okada M . Treatment-free remission after first-line dasatinib discontinuation in patients with chronic myeloid leukaemia (first-line DADI trial): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2020; 7(3):e218-e225. DOI: 10.1016/S2352-3026(19)30235-2. View