Zheng Zhenxiang, Tang Hao, Zhang Xinxia, Zheng Liling, Yin Zhao, Zhou Jie, Zhu Yangmin
Jinan University, Guangzhou, 510632, Guangdong, China.
Department of Hematology, Guangdong Second Provincial General Hospital, Jinan University, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, 510317, Guangdong, China.
Discov Oncol. 2024 Oct 23;15(1):586. doi: 10.1007/s12672-024-01444-9.
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.
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.
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).
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.
https://www.crd.york.ac.uk/prospero/ (Registration No. CRD42023471334).
无治疗缓解（TFR）是慢性期慢性髓性白血病（CML-CP）部分患者治疗的新长期目标。然而，尚未确定可尝试实现TFR的合适患者群体及其影响因素。本荟萃分析旨在探讨在停用酪氨酸激酶抑制剂（TKIs）前达到深度分子反应（DMR）的CML-CP患者中的TFR情况，并探讨影响TFR的可能因素及停药安全性。
我们进行了一项系统评价和单臂荟萃分析，通过在PubMed、Embase、Web of Science、Cochrane图书馆和中国知网数据库中系统检索截至2023年9月发表的文献。使用MINORS量表进行评估。采用随机效应模型计算结局指标，包括12个月和24个月时的总体平均TFR率以及亚组差异。数据合成与分析使用Stata17.0软件完成。
本荟萃分析共纳入19项涉及2336例患者的单臂试验，12个月时总体平均TFR率为59%[95%CI：0.56 - 0.63]，24个月时为55%[95%CI：0.52 - 0.59]，且在TFR期间未报告与CML相关的病情恶化或死亡。我们的亚组分析显示，更好的TFR与既往干扰素治疗（P = 0.003）以及分子反应深度MR5.0（P = 0.020）相关。
我们的研究表明，既往干扰素治疗以及达到MR5.0或更高的分子反应深度与更高的TFR率相关，达到MR5.0或更高的患者在停用TKI后的第二年TFR率高达62%。考虑到纳入试验的高度异质性，上述影响仍需在未来的停药试验中进一步验证和进行更详细的亚组分析。
