Prognostic factors for maintenance of molecular remission after TKI discontinuation in CML patients

August 2023 CongressUpdate Andrea Enguita

During the 2023 European Haematology Association (EHA) congress, novel findings of the EURO-SKI trial shed light on the prognostic factors impacting molecular remission maintenance after tyrosine kinase inhibitor (TKI) treatment discontinuation in patients with chronic myeloid leukaemia.

The goal of discontinuing long-term therapy with tyrosine kinase inhibitors (TKIs) has become feasible for an increasing number of patients with chronic phase chronic myeloid leukaemia (CP-CML). The EURO-SKI trial, conducted across eleven countries, represents one of the largest studies addressing TKI treatment discontinuation in CML patients.1


This new analysis of the EURO-SKI trial aimed at the identification of prognostic factors associated with maintaining molecular relapse-free survival three years after stopping TKI treatment. The trial included patients who had received first-line or second-line (due to toxicity to first-line) TKI treatment for at least three years, had the transcripts e13a2a and/or e14a2, and were in MR4 (BCR:ABL≤ 0.01) for at least one year. TKI treatment was discontinued upon confirming the MR4 status, followed by routine RQ-PCR analyses over three years to assess molecular response.

Study findings

A total of 510 patients from the EURO-SKI trial were included in the prognostic modelling at 3 years, as well as 184 patients from the STIM 2 trial for validation. At 36 months, 45% and 41% of the STIM 2 and EURO-SKI cohorts achieved a major molecular response (MMR) maintenance rate, respectively. Univariate analysis identified several significant factors associated with a higher probability of having a maintained MMR at 3 years. This includes a longer duration of TKI treatment (OR=1.124), a longer duration of a deep molecular response (DMR) under TKI therapy (OR=1.102), and the presence of the e14a and e13a2 transcript types compared to e13a2 alone (OR=2.064). Additionally, a higher blast ratio at the time of diagnosis was associated with a lower likelihood of maintaining MMR at 3 years (OR=0.889). These findings were confirmed by the STIM 2 trial. Multiple modelling revealed three significant models in the EURO-SKI trial, including the duration of TKI treatment combined with blast ratio at diagnosis (model a) or transcript type (model b). Model c included DMR duration under TKI, time to DMR under TKI, and blasts in peripheral blood. Only the first two models were confirmed by the STIM 2 trial.2


In summary, this analysis identified four prognostic factors for MMR maintenance: duration of TKI treatment, DMR duration under TKI treatment, transcript type, and the number peripheral blasts at diagnosis. These factors were further confirmed in univariate modelling by the STIM 2 trial. In addition to the duration of TKI treatment, transcript type and peripheral blasts at diagnosis were prognostic factors for MMR maintenance also in multiple modelling.2


  1. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747-57.
  2. Pfirrmann M. Prognostic factors for 3-year major molecular response maintenance in chronic myeloid leukaemia patients in the european stop kinase inhibitors (EURO-SKI) trial. Presented at EHA 2023; Presentation ID S155.