Discontinuation Of Tyrosine Kinase Inhibitors In Patients With Chronic Myeloid Leukemia:a Meta-Analysis

Objective:To systematically evaluate the safety and feasibility of discontinuing tyrosine kinase inhibitors(TKI)in patients with chronic myeloid leukemia(CML)who have obtained a long-lasting deep molecular response(DMR),and provide a reference for clinical treatment.Methods:The PubMed and Embase databases were searched,and all the patients with chronic myeloid leukemia were selected who obtained a deep molecular response and the TKI were stopp.After extracting the data,the R software was used for meta-analysis.Results:A total of 950 articles were searched and 17 valid articles were included.A total of2209 patients were treated with TKI for at least 2 years,and patients with deep molecular response(MR4 or higher)at least 1 year of CML chronic/accelerate phase were discontinued.The relapse rate at 6 months after discontinuation of TKI was 28% [95% CI(22%;35%),and the relapse rate at 12 months was 30% [95% CI(24%;37%),the overall relapse rate was 44% [95% CI(39%;49%)];the relapse rate of the first-generation TKI after discontinuation was 46% [95% CI(38%;54%)],and the relapse rate after the second-generation TKI was 45%[95%CI(41%;49%)];the number of relapses at 6 months of discontinuation accounted for 82% [95% CI(73%;88%)] of overall relapses,and the number of relapses at 12 months of discontinuation accountedfor 87% [95% CI(82%;91%)] of the overall number of relapses;The probability of regaining MR3.0 after retreatment was 95% [95% CI(92%;97%)],and the probability of regaining MR4.0 was 85% [95% CI(79%;90%)];Patients who had previously received interferon(IFN)treatment had a lower relapse rate after discontinuation of treatment than patients without a history of interferon therapy(RR=0.58 [95% CI(0.43;0.77)],P=0.0001),while Socal score and gender has no significant effect on relapse rate.Conclusion:56% of patients with chronic myeloid leukemia who achieved persistent deep molecular response to MR4.0 and maintained for at least 1 year after TKI treatment for at least 2 years can obtain treatment-free remission after drug withdrawal,and most of the molecular relapse occurred within 1 year after discontinuation.The majority of the relapsed patients can regain the major molecular response after re-treatment.Previous IFN treatment favored the maintenance of treatment-free remission after discontinuation of TKI.