Given the durability of tyrosine kinase inhibitor (TKI)–induced deep molecular responses (DMRs), the goals of therapy in CML have evolved to include TFR in selected patients. Attempting TFR is currently recommended for those in chronic-phase CML who have been on TKI therapy for at least 3 years and have had a sustained DMR for at least 2 years.

These recommendations are based on the inclusion criteria that are used in multiple large TFR studies. Several studies of TFR that were presented at EHA2023 were based on data from the phase 3 EURO-SKI trial. This trial was designed to evaluate molecular recurrence-free survival after stopping TKI therapy in a large pan-European cohort of patients with CML and to identify prognostic markers to increase the rate of patients in durable DMR after stopping TKI therapy.

At EHA2023, prognostic factors that were associated with major molecular response (MMR) maintenance at 3 years after imatinib discontinuation were reported by Pfirrmann and colleagues in abstract S155. The study group included 218 patients with CML who received first-line imatinib treatment without interferon-α pretreatment. Researchers reported that, at 36 months, 41% of patients were still in MMR. Factors associated with MMR maintenance at 36 months on univariate analysis were longer duration of TKI treatment, longer duration of DMR while receiving TKI therapy, and fewer blasts. “It is remarkable that blasts at diagnosis still played a role in good molecular responders, just as in survival of all patients in chronic phase,” the authors concluded. Follow-up studies will address the differences between the early and late losses of MMR and the development of a prognostic score for stable MMR. A 2022 study from MD Anderson Cancer Center reported an estimated 5-year TFR rate of 87% when treatment discontinuation was attempted after at least 5 years of DMR.

The health-related quality-of-life (HRQOL) benefits of stopping long-term TKI therapy may be greater in younger patients with CML compared with older individuals with CML, according to an analysis of HRQOL outcomes in patients enrolled in the EURO-SKI trial. At EHA2023, Efficace et al presented findings from their study of 686 patients who were enrolled in EURO-SKI and completed HRQOL assessments at baseline and periodically up to 12 months after TKI discontinuation (abstract S159). The patients were divided into the following age group categories: 18 to 39 years (n=62), 40 to 59 years (n=272), 60 to 69 years (n=209), and 70 years and older (n=143). Patients in the 2 youngest age groups (ie, 18-39 years and 40-59 years) typically reported the greatest HRQOL benefits from treatment discontinuation across multiple functional and symptom measures, including a statistically significant decrease in the burden of fatigue over time, a finding that was not demonstrated in the 2 oldest age groups. Among patients without relapse, the percentage of those who reported a deterioration in physical functioning between baseline and 6 months was 16%, 44%, 47%, and 65% in patients aged 18 to 39 years, 40 to 59 years, 60 to 69 years, and 70 years and older, respectively. This study has shown that the younger we are, the more we benefit from treatment discontinuation. Stopping TKI therapy provides tremendous benefits in the younger population.