Treatment-free remission (TFR) — stopping TKI therapy while maintaining molecular remission — has become a major therapeutic goal in CML management.
Guidelines recommend that selected chronic phase CML patients in stable deep molecular response (DMR) may consider discontinuing TKI under frequent monitoring.
Eligibility requires: First-line therapy (or second-line if intolerance was the only reason for switching)
Typical BCR::ABL1 transcripts
TKI therapy duration >5 years (>4 years for 2nd-generation TKIs)
DMR (MR4 or better-BCR::ABL1 ≤0.01% sustained for >2 years. No prior treatment failure 
The median TFR duration was 14.6 months, with 63% of patients actively remaining in TFR at a median follow-up of 21 months.
TFR was lost by 54% of patients in the first 6 months, 16% between 6–12 months, and smaller proportions thereafter. 
In the GIMEMA CML 0307 trial of nilotinib, among patients who achieved stable DMR and discontinued, the estimated 2-year treatment-free survival was 72.6%. 
Second-Generation TKIs 2G-TKIs (dasatinib, nilotinib) can induce faster and more sustained DMRs, and patients may become eligible for TFR after a shorter overall treatment duration, as demonstrated in studies. 
There is minimal data on TFR after discontinuation of the novel STAMP inhibitor asciminib.
Recent case reports demonstrate that sustained TFR after asciminib discontinuation is feasible, including in patients intolerant to multiple ATP-competitive TKIs who achieved DMR on asciminib.
Some patients experience musculoskeletal symptoms (myalgia, arthralgia) after stopping TKIs — this TKI withdrawal syndrome is distinct from molecular relapse and typically self-limiting.
Patients who lose TFR and restart their TKI almost universally regain molecular response, so discontinuation attempts are considered safe with appropriate monitoring.
Guidelines recommend that selected chronic phase CML patients in stable deep molecular response (DMR) may consider discontinuing TKI under frequent monitoring.
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