Saussele S, et al. - Authors wanted to identify precise conditions for stopping tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia. Good molecular relapse-free survival was seen in patients with chronic myeloid leukemia who achieved deep molecular responses. TKI discontinuation should be considered in these patients, especially those who have sustained deep molecular response for a long time. Patients could be spared from treatment-induced side-effects and health expenditure could be reduced by stopping the treatment.

Methods

• Researchers enrolled patients in this prospective, non-randomized trial with chronic myeloid leukemia at 61 European centers in 11 countries.
• The patients that were eligible had chronic-phase chronic myeloid leukemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year.
• Molecular relapse-free survival, defined by loss of major molecular response (MMR; >0.1% BCR-ABL1 on the International Scale) and assessed in all patients with at least one molecular result was the primary endpoint.
• A prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples and the cost impact of stopping TKI therapy were the secondary endpoints.
• Loss of hematological response, progress to accelerated-phase chronic myeloid leukemia, or blast crisis were considered serious adverse events.
• The results of the prespecified interim analysis were presented in this study, which was done after the 6-month molecular relapse-free survival status was known for 200 patients.

Results

• As per data, experts evaluated 868 patients with chronic myeloid leukemia for eligibility between May 30, 2012, and Dec 3, 2014, of whom 758 were enrolled.
• Median follow-up was 27 months for the 755 patients evaluable for molecular response (IQR 21–34).
• Results demonstrated that, for these patients, molecular relapse-free survival was 61% (95% CI 57–64) at 6 months and 50% (46–54) at 24 months.
• Out of these 755 patients, 371 (49%) lost MMR after TKI discontinuation, four (1%) died while in MMR for reasons not related to chronic myeloid leukemia (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted TKI therapy while in MMR.
• In chronic-phase chronic myeloid leukemia after loss of MMR and re-initiation of TKI therapy, a further 6 (1%) patients died for reasons unrelated to chronic myeloid leukemia, and 2 (<1%) patients lost MMR, despite restarting TKI therapy.
• Data showed that in the prognostic analysis in 405 patients who received imatinib as first-line treatment (learning sample), there was an association of longer treatment duration (odds ratio [OR] per year 1.14 [95% CI 1.05–1.23]; p=0.0010) and longer deep molecular response durations (1.13 [1.04-1.23]; p=0.0032) with increasing probability of MMR maintenance at 6 months.
• For deep molecular response duration, the OR was replicated in the validation sample consisting of 171 patients treated with any TKI as first-line treatment, although the association was not significant (1.13 [0.98–1.29]; p=0.08).
• TKI discontinuation was linked to a substantial cost savings (an estimated €22 million).
• They did not report any serious adverse events.