Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
- Study type
- Clinical trial
- Study name
- EURO-SKI
- Design
- Prospective, multicentre, non-randomised trial (prespecified interim analysis) at 61 European centres in 11 countries
- Sample size
- 758 patients enrolled (of 868 screened); 755 patients evaluable for molecular response
- Source
- The Lancet Oncology · 2018
- Trial registration
- NCT01596114
In plain words
Some people with chronic myeloid leukaemia who have been treated for years with tyrosine kinase inhibitor drugs, and whose disease has fallen to a very low level on molecular tests, can stop their medicine. In this study, about half of patients were still free of molecular relapse two years after stopping. In the others, the molecular response was lost and treatment was started again. Stopping the medicine should only be done on a doctor's advice and with regular molecular testing.
Key results
Treatment arms and regimens
No new drug: complete discontinuation of the tyrosine kinase inhibitor (TKI) in patients with at least 3 years of treatment and at least 1 year of deep molecular response (at least MR4, confirmed in a EUTOS-standardised laboratory), with regular BCR::ABL1 molecular monitoring; discontinuation continued until loss of major molecular response (MMR), after which the TKI was restarted.
Source of the regimen details: Intervention: treatment discontinuation (no new drug); abstract of the paper and ClinicalTrials.gov NCT01596114 (inclusion criteria and the rule for restarting treatment after loss of MMR)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged 18 years and older with chronic-phase chronic myeloid leukaemia (CML) who had received any tyrosine kinase inhibitor (TKI) for at least 3 years (first line, second line because of first-line toxicity, or a combination; without treatment failure according to ELN recommendations) and had a confirmed deep molecular response for at least 1 year. A history of or plan for allogeneic stem cell transplantation was an exclusion criterion (ClinicalTrials.gov).
Endpoints
Primary endpoint: molecular relapse-free survival, defined by loss of major molecular response (MMR; BCR-ABL1 above 0.1% on the International Scale) and assessed in all patients with at least one molecular result.
Secondary endpoints: prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples, and the cost effect of stopping TKI therapy. Loss of haematological response or progression to accelerated phase or blast crisis was considered a serious adverse event.
Safety and side effects
No serious adverse events were reported. The recorded deaths were from causes unrelated to chronic myeloid leukaemia (myocardial infarction, lung cancer, kidney cancer and heart failure).
Clinical significance and place in guidelines
This study shows that stopping a TKI is feasible in selected patients with a stable deep molecular response and can reduce treatment side effects and costs, particularly in patients who have been in deep molecular response for longer. According to the abstract, these results come from an interim analysis of a non-randomised study. The status of the recommendation in clinical guidelines and implementation issues (such as regular molecular monitoring and restarting treatment) should be checked separately.
Limitations
The study is non-randomised without a control group, and the results come from an interim analysis; the study is still ongoing. In the validation sample, the association of deep molecular response duration with MMR maintenance was not significant (p=0.08).
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.