The duration of tyrosine kinase inhibitor (TKI) treatment can predict both early and late recurrence in patients with chronic myeloid leukemia (CML) who discontinue TKIs, according to the final analysis of the phase 3 EURO-SKI trial.
Both TKI duration and duration of deep molecular response were associated with loss of major molecular response (MMR) at 6 months. However, only TKI duration was associated with recurrence between 6 months and 36 months.
The underlying mechanisms of late recurrence must be investigated further, according to EURO-SKI investigator Francois-Xavier Mahon, MD, PhD, of Institut Bergonié in Bordeaux, France, and colleagues.
Dr Mahon presented the updated results from the trial at the 2021 American Society of Hematology (ASH) Annual Meeting.
The main goal of EURO-SKI (ClinicalTrials.gov Identifier: NCT01596114) was to define prognostic markers to increase the proportion of patients in deep molecular response after stopping TKI treatment.
The study included 728 patients with CML who were in molecular response 4 (MR4) for at least 1 year and had received TKI treatment for at least 3 years. The patients’ median age at diagnosis was 52 years (range, 11-85 years), and 46.8% were women.
The median duration of TKI treatment was 7.5 years (range, 3.0-14.1 years). Before stopping treatment, patients were in MR4 for a median of 4.7 years (range, 1.0-13.3 years).
The first and second primary endpoints were MRecFS at 6 months and 36 months, respectively. The null hypotheses were that MRecFS would be less than or equal to 40% at 6 months and less than or equal to 35% at 36 months.
The MRecFS rate was 62% at 6 months, 55% at 12 months, and 46% at 36 months, so the null hypotheses were rejected (P <.0001 for both).
The molecular recurrence treatment-free survival rate was 61% at 6 months, 54% at 12 months, and 45% at 36 months.
The proportion of patients with MMR loss was 38% at 6 months, 44% at 12 months, and 50% at 36 months, which meant 12% of patients lost MMR from month 6 to 36.
There were 9 patients who died without loss of MMR (not CML-related deaths) and 15 patients who restarted TKI treatment without MMR loss.
Analyses confirmed that TKI treatment duration and the duration of deep molecular response were still “the most important factors” for predicting MMR loss at 6 months, Dr Mahon said.
However, for MMR loss between 6 months and 36 months, the duration of TKI treatment was the only relevant variable in a univariate analysis.
“Further prognostic analysis will follow,” Dr Mahon said.
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Mahon FX, Richter J, Hochhaus A, et al. Final analysis of a PAN European STOP tyrosine kinase inhibitor trial in chronic myeloid leukemia: The EURO-SKI study. Presented at ASH 2021; December 11-14, 2021. Abstract 633.