In a report in the Journal of Clinical Oncology, Francois-Xavier Mahon, MD, PhD, and colleagues provided the final analysis of the European Stop Kinase Inhibitors (EURO-SKI) study. The trial evaluated the effect of stopping tyrosine kinase inhibitor (TKI) treatment in patients with chronic myeloid leukemia (CML) in stable deep molecular remission (DMR)—and identified factors associated with maintained major molecular response (MMR).
Francois-Xavier Mahon, MD, PhD
Study Details
The study involved adult patients with CML in chronic phase on TKI treatment for ≥ 3 years with confirmed DMR (defined as BCR::ABL1-transcripts ≤ 0.01% on the International Scale for ≥ 12 months) who stopped TKI treatment. The primary outcome measures were maintenance of MMR (BCR::ABL1 ≤ 0.1%) 6 and 36 months after stopping TKIs.
Key Findings
A total of 434 (61%, 95% confidence interval [CI] = 57%–64%) of 728 evaluable patients remained in MMR at 6 months after stopping TKI treatment. A total of 309 (46%, 95% CI = 42%–49%) of 678 evaluable patients remained in MMR at 36 months after stopping TKI treatment.
Longer duration of TKI treatment (odds ratio [OR] = 1.12) and longer duration of DMR (OR = 1.13) before stopping TKI treatment were significantly associated with MMR maintenance at 6 months. Type of BCR::ABL1 transcript was also identified as a prognostic factor; MMR maintenance was significantly more likely among patients with transcript type e14a2 alone or in combination with e13a2 vs those with only transcript type e13a2 (OR = 1.89, P = .0043).
Factors significantly associated with MMR maintenance between 6 and 36 months included duration of TKI treatment (but not DMR duration) before stopping TKI treatment and disease characteristics at diagnosis, including peripheral blood blast cells percentage and platelet counts.
Multivariate analysis of factors in MMR maintenance over the total 36-month trial period showed independent effects of duration of TKI treatment (OR = 1.11, P = .016,), duration of DMR while receiving TKI (OR = 1.12, P = .0149), percentage of peripheral blood blast cells at diagnosis (OR = 0.88, P = .011), and transcript type. Patients with BCR::ABL1 transcript type e14a2 alone or with 1e13a2 had a higher probability of maintaining MMR over 36 months vs those with e13a2 alone (OR = 2.09, P = .0047).
The investigators concluded, “In addition to the duration of treatment, transcript type as well as blasts in peripheral blood at diagnosis should be considered as important factors to predict treatment-free remission.”
Dr. Mahon, of Bergonié Cancer Institute, INSERM, University of Bordeaux, France, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the European Leukemia Net (ELN) and French National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
