Treatment-free remission outcomes in pediatric chronic myeloid leukemia: Second-generation TKIs vs. Imatinib–a real-world multicenter study from China

Abstract

Abstract Background Studies have demonstrated that a subset of adult chronic myeloid leukemia (CML) patients achieving deep molecular response (DMR) for ≥2 years with tyrosine kinase inhibitor (TKI) therapy can successfully discontinue treatment and maintain treatment-free remission (TFR), thereby reducing long-term drug toxicity and financial burden. However, data on TFR in pediatric CML remain limited, particularly regarding whether second-generation TKIs (e.g.,nilotinib, dasatinib) confer superior TFR rates compared to first-generation imatinib (IM) in real-world pediatric populations. Methods This retrospective multicenter study analyzed clinical data from 54 CML chronic-phase patients aged <18 years who discontinued TKI therapy between September 2016 and September 2024 across nine Chinese hematology centers.Patients were stratified into IM and second-generation TKI groups based on pre-discontinuation therapy.Baseline characteristics were compared using Mann-Whitney U and χ² tests,TFR rates were analyzed via log-rank test. Results The cohort included 27 males and 27 females.Median ages at diagnosis and TKI discontinuation were 13years and 20years, respectively.Pre-discontinuation therapy comprised IM in 39 patients (72.2%) and second-generation TKIs in 15(27.8%;nilotinib[n=9],dasatinib[n=5],flumatinib [n=1]).Median time from TKI initiation to DMR:18 (IQR10–32) months,Median TKI treatment duration pre-discontinuation:96 (IQR78–118) months,Median DMR duration pre-discontinuation: 72(IQR56–92) months,No significant differences were observed between IM and second-generation TKI groups in baseline characteristics (all P>0.05).After a median follow-up of 46(IQR16–63) months post-discontinuation,21 patients (38.9%) lost major molecular response (MMR) at a median of 8 (IQR3–14) months,with an overall TFR rate of 61.1%.Among relapse cases,20/21(95.2%) regained DMR after median 5(IQR3–14) months of TKI reinitiation.IM group: 12-/24-month TFR rates 63.6%/59.4%;overall TFR 56.4%,Second-generation TKI group ：12-/24-month TFR rates 72.7%;overall TFR 73.3%,Second-generation TKIs showed higher TFR rates this difference lacked statistical significance (P=0.127). Conclusion Real-world data suggest that TFR is achievable in pediatric CML, with a trend toward superior TFR rates with second-generation TKIs compared to IM. Keywords pediatric CML,treatment-free remission,tyrosine kinase inhibitors,imatinib, second-generation TKIs.