Outcomes After Discontinuation of Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia

Key Points

  • Molecular relapse-free survival was 61% at 6 months and 50% at 24 months.
  • Longer duration of deep molecular response was associated with increased 6-month MMR rate.

In an interim analysis of a European trial reported in The Lancet Oncology, Saussele et al found that discontinuation of tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia (CML) with deep molecular response was associated with good molecular relapse-free survival, particularly among patients with longer major molecular response (MMR).

Study Details

The prospective study (EURO-SKI) included 755 evaluable patients with chronic-phase CML enrolled from 61 sites in 11 European countries between May 2012 and December 2014 who had received any tyrosine kinase inhibitor for ≥ 3 years without treatment failure and had a confirmed deep molecular response for ≥ 1 year.

The primary endpoint was molecular relapse-free survival after discontinuation of tyrosine kinase inhibitor treatment, defined by loss of MMR (> 0.1% BCR-ABL1). The current report provides findings in a prespecified interim analysis performed after 6-month molecular relapse-free survival status was known for 200 patients.

Median follow-up for the 755 patients evaluable for molecular response was 27 months after tyrosine kinase inhibitor discontinuation. Molecular relapse-free survival was 61% at 6 months and 50% at 24 months.

A total of 371 patients (49%) lost MMR after tyrosine kinase inhibitor discontinuation, 4 (1%) died while in MMR for reasons unrelated to CML (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted tyrosine kinase inhibitor therapy while in MMR. A further 6 (1%) patients died after loss of MMR and reinitiation of tyrosine kinase inhibitor therapy for reasons unrelated to CML, and MMR was lost despite reinitiation of tyrosine kinase inhibitor treatment in 2 patients (< 1%).

In a learning sample consisting of 405 patients who received imatinib as first-line treatment, longer treatment duration (odds ratio [OR] per year = 1.14, P = .0010) and longer duration of deep molecular response (OR = 1.13, P = .0032) were associated with increased likelihood of MMR persistence at 6 months. In a validation sample consisting of 117 patients receiving any tyrosine kinase inhibitor as first-line treatment, duration of deep molecular response was associated with persistence of MMR at 6 months, although the association failed to achieve significance (OR = 1.13, P = .08). Tyrosine kinase inhibitor discontinuation was associated with cost savings amounting to an estimated €22 million.

The investigators concluded, “Patients with chronic myeloid leukemia who have achieved deep molecular responses have good molecular relapse-free survival. Such patients should be considered for tyrosine kinase inhibitor discontinuation, particularly those who have been in deep molecular response for a long time. Stopping treatment could spare patients from treatment-induced side-effects and reduce health expenditure.”

The study was funded by the European LeukemiaNet Foundation and France National Cancer Institute.

Francois-Xavier Mahon, MD, of Institut Bergonié, Bordeaux, is the corresponding author for The Lancet Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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