A second discontinuation attempt of tyrosine kinase inhibitor (TKI) therapy may be safe and feasible among patients with chronic myeloid leukemia (CML), according to research published in Cancer.1

Patients with CML who have a deep molecular response (DMR) to TKI therapy may attempt therapy discontinuation, though molecular relapse is common, occurring in 50% of cases. Little is known about whether a second discontinuation attempt is feasible.

For the multi-center RE-STIM study, researchers enrolled 70 patients who failed first-attempt TKI discontinuation to determine treatment-free remission (TFR) after a second attempt.

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At diagnosis, the median age was 51 years and all patients received imatinib, alone or combined with interferon-alpha or cytarabine, in the first line. Patients were treated with a TKI for a median of 59 months prior to discontinuation.

Necessary criteria for discontinuation were at least 3 year exposure to imatinib, sustained MR4.5 for at least 2 years, and undetectable BCR­ABL1 transcripts for at least 2 years.

The median time to loss of molecular response was 3 months; the median time to TKI re-initiation was 5 months.

At the second discontinuation attempt, the median patient age was 60 years and the median time from re-initiation to second attempt was 32 months.

At a median follow-up of 38.3 months, 45 of the 70 patients (64.3%) lost major molecular response a median of 5.3 months after second discontinuation. TFR rates were 48% at 12 months, 42% at 24 months, and 35% at 36 months. No patients progressed to blast phase.

Patients who maintained DMR for 3 months after the first discontinuation attempt had a better TFR rate after the second attempt.

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The authors concluded that while a second TKI discontinuation attempt is feasible, “…close and prolonged molecular monitoring is required. To confirm the long-term safety of this strategy, patients should be registered or included in a prospective trial.”


  1. Legros L, Nicolini FE, Etienne G, et al. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer. 2017 Jul 27. doi:  10.1002/cncr.30885 [Epub ahead of print]