40% to 50% of patients are eligible to attempt TFR⁴
and 50% to 60% of patients treated with 2G TKIs can sustain TFR⁴

Criteria for TKI Discontinuation: according to NCCN CML 2026⁵

• CP-CML. No prior history of AP-CML or BP-CML.
• On approved TKI therapy for at least 3 years.^a,b
• Prior evidence of quantifiable BCR::ABL1 transcript.
• Stable molecular response (MR4; BCR::ABL1 ≤0.01% ^IS) for ≥2 years, as documented on at least 4 tests, performed at least 3 months apart.^b
• Access to a reliable qPCR test with a sensitivity of detection of at least MR4.5 (BCR::ABL1 ≤0.0032% ^IS) and that provides results within 2 weeks.
• Molecular monitoring every 1–2 months for the first 6 months following discontinuation, bimonthly during months 7–12, and quarterly thereafter (indefinitely) for patients who remain in MMR (MR3; BCR::ABL1 ≤0.1% ^IS).
• Prompt resumption of TKI within 4 weeks of a loss of MMR with monthly molecular monitoring until MMR is re-established, then every 3 months thereafter is recommended indefinitely for patients who have reinitiated TKI therapy after a loss of MMR. If MMR is not achieved after 3 months of TKI resumption, BCR::ABL1 kinase domain mutation testing should be performed, and monthly molecular monitoring should be continued for another 6 months.

a The feasibility of TFR following discontinuation of TKIs other than dasatinib, imatinib, or nilotinib has not yet been evaluated in clinical studies. It is reasonable to assume that the likelihood of TFR following discontinuation would be similar irrespective of TKI in patients who have achieved and maintained DMR (MR4.0; ≤0.01% BCR::ABL1 IS) for ≥2 years, based on the extrapolation of findings from the studies that have evaluated TFR following discontinuation of imatinib, dasatinib, or nilotinib.

b Disease characteristics at diagnosis, blast cell and platelet count in peripheral blood, a higher Sokal risk score, female gender, lower natural killer (NK) cell counts, suboptimal response or resistance to imatinib, duration of TKI therapy and DMR prior to TKI discontinuation have been identified as independent factors predictive of recurrence after TKI discontinuation. In the EURO-SKI study, only the duration of TKI therapy prior to discontinuation was significantly associated with the maintenance of MMR at 36 months after TKI discontinuation (Mahon FX, et al. J Clin Oncol 2024;42:1875-1880). Lack of MR4.0 at 36 months after discontinuation of TKI was highly predictive of subsequent loss of MMR (Richter J, et al. Leukemia 2021;35:2416-2418).

Adapted from ref 5 and 6

Adherence is important for achieving responses such as MMR and CMR, which are essential for disease control and TFR eligibility⁷