TKI Discontinuation Supports Long-Term Treatment-Free Remission in Chronic-Phase CML

Key Clinical Summary

• Approximately half of adults with chronic-phase chronic myeloid leukemia (CML) maintained treatment-free remission (TFR) for up to 36 months after discontinuing tyrosine kinase inhibitor (TKI) therapy.
• A systematic review and meta-analysis of 16 studies (2156 patients) found pooled TFR rates of 60% at 6 months, 55% at 12 months, 54% at 24 months, and 52% at 36 months.
• Longer TKI treatment duration was associated with higher 6-month TFR rates, supporting current recommendations for sustained deep molecular remission before TKI discontinuation.

TFR after TKI discontinuation remains a key therapeutic goal for patients with chronic-phase CML. A systematic review and meta-analysis of prospective and observational studies found that approximately half of eligible patients maintained long-term TFR following TKI cessation. The findings also identified longer TKI exposure as a predictor of improved short-term TFR outcomes.

TFR Rates Remain Stable Beyond the First Year

Investigators systematically searched PubMed, Embase, and Scopus from database inception through August 31, 2025, to identify prospective and observational studies evaluating TFR after TKI discontinuation in adults with chronic-phase CML.

A total of 16 studies involving 2156 patients met the inclusion criteria. Using a random-effects meta-analysis, investigators pooled TFR rates at multiple time points following TKI discontinuation.

The pooled TFR rate was 60% (95% CI, 54%-65%) at 6 months, declining to 55% (95% CI, 49%-60%) at 12 months. Longer-term outcomes remained relatively stable, with pooled TFR rates of 54% (95% CI, 48%-59%) at 24 months and 52% (95% CI, 45%-59%) at 36 months.

Substantial heterogeneity was observed across studies, with I² values exceeding 80% for all pooled analyses. According to the review, most molecular relapses occurred within the first 12 months after discontinuation.

Meta-regression demonstrated a positive association between longer TKI duration and improved 6-month TFR outcomes, described by the equation: TFR6mo = 0.0835 + 0.2744 × log10(median TKI duration, months). Risk of bias was assessed using the Newcastle–Ottawa Scale, and the certainty of evidence for all reported outcomes was graded as moderate using the GRADE framework.

Results Reinforce Current TKI Discontinuation Strategies

The findings indicate that TFR is an achievable long-term goal for approximately half of appropriately selected patients with chronic-phase CML who discontinue TKI therapy. The relatively stable TFR rates between 12 and 36 months suggest that patients who remain in remission beyond the first year may have sustained long-term benefit.

The analysis also reinforces the importance of treatment duration before discontinuation. The observed association between longer TKI exposure and improved early TFR supports existing guideline recommendations to ensure patients achieve durable deep molecular remission before attempting treatment discontinuation.

Because most relapses occurred during the first year after stopping therapy, the results also underscore the need for careful patient selection and close molecular monitoring during this period. Although substantial heterogeneity across studies suggests variation in patient populations and study designs, the moderate certainty of evidence supports the feasibility of TFR as a realistic treatment objective in chronic-phase CML.

Authors Emphasize Careful Monitoring After TKI Cessation

The study authors concluded that "approximately half of patients with chronic-phase CML who discontinue TKI therapy sustain long-term TFR." They further reported that longer TKI exposure was associated with greater TFR success, supporting current guideline recommendations to establish durable deep molecular remission before discontinuation. The authors also emphasized that these findings reinforce the feasibility of TFR while highlighting the importance of careful patient selection and close monitoring.

Long-Term Data Support TFR in Eligible Patients

TFR following TKI discontinuation appears feasible for approximately one-half of patients with chronic-phase CML who meet discontinuation criteria. The findings support longer TKI treatment before cessation and continued close monitoring after discontinuation, particularly during the first year when most relapses occur.

Reference

Tungjitviboonkun S. Molecular remission after tyrosine kinase inhibitor cessation in chronic myeloid leukemia (CML): a systematic review and meta-analysis. Presented at: ASCO 2026; May 29-June 2, 2026. Chicago, IL.