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

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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).
Funding Information
  • Key Program for the National Natural Science Foundation of China (82304901, 82202034)
  • Guangdong Basic and Applied Basic Research Foundation (2021A1515110430)
  • Scientific Research Project Program of Sichuan Medical Association (S20038)
  • Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome
  • Guangzhou Science and Technology Plan Project (2023A03J0262, 2024A03J0991, 2024A04J4325)
  • Foundation of Guangdong Second Provincial General Hospital (YN2023-001, TJGC-2023002)

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