SAN DIEGO Among patients with chronic myeloid leukemia in chronic phase (CML-CP), tyrosine kinase inhibitors (TKIs) can be safely and successfully discontinued a second time despite failing first discontinuation, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1

“Several studies provide evidence that patients with deep and sustained molecular responses may remain free from treatment after first- or second-generation TKI discontinuation,” said lead investigator Laurence Legros, MD, PhD, Fi-LMC group, Pessac, France. “Our goal was to evaluate the feasibility and safety of a second TKI discontinuation in patients who failed first discontinuation attempt and subsequently regained a deep molecular response after TKI re-challenge.”

For the study, researchers analyzed data from 69 adult patients without prior allogeneic transplantation or progression to advanced phase CML undergoing a second attempt of TKI discontinuation after a first failure of TKI cessation.

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After a median follow-up of 39 months, researchers found that no patients transformed to accelerated phase or blast crisis, and there were no CML-related deaths.

Twenty-five patients are free of treatment as of the last follow-up, including 12 patients in sustained undetectable molecular disease, 12 with intermittent positive BCR-ABL transcript detection without major molecular response loss, and 1 patient who lost major molecular response but declined TKI re-challenge.

Forty-four patients are currently in TKI re-challenge, with 16 patients switching TKIs at re-challenge and 29 regaining undetectable molecular disease within a median of 7 months.

“Around 40% of patients remain free of treatment at 24 months after second TKI discontinuation,” Dr Legros added. “Molecular relapses extended later over time in comparison to other treatment-free remission studies, leading to a drop to 33% at and beyond 36 months.”

Age at second discontinuation, Sokal risk score, TKI duration at first discontinuation, total TKI duration, total undetectable molecular disease duration, type of TKI at first discontinuation, and reason for first TKI re-challenge were not associated with major molecular loss after second TKI discontinuation.

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“We conclude that a second attempt of TKI therapy discontinuation can be safely proposed in patients with deep and stable undetectable BCR-ABL transcripts under close molecular monitoring,” said Dr Legros.


  1. Pagliardini T, Nicolini FE, Giraudier S, et al. Second TKI discontinuation in CML patients that failed first discontinuation and subsequently regained deep molecular response after TKI re-challenge. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.