Long-term follow-up of treatment-free remission in chronic myeloid leukemia after discontinuation of tyrosine kinase inhibitor therapy.

6566 Background: Treatment-free remission (TFR) is an important goal of therapy in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP). Here, we report our TFR experience in pts with CML-CP after a longer follow-up. Methods: Pts with CML-CP who were treated with tyrosine kinase inhibitors (TKIs) and subsequently discontinued therapy between October 2011 and January 2024 were included in this analysis. Molecular responses were assessed by qPCR (MMR, MR4, and MR4.5 defined as BCR::ABL1 transcripts ≤0.1%, ≤0.01%, and ≤0.0032% on the international scale, respectively). The Kaplan Meier method was used to estimate the probability of TFR. Results: A total of 351 pts with CML-CP discontinued TKI therapy after a median treatment duration of 118.5 mo (range, 15.8-303.2). Most of the pts opted for elective discontinuation (70.2%) or discontinued therapy due to adverse events (24.3%). The median duration of sustained MR4.5 before TKI discontinuation was 61.8. mo (range, 1.0-206.8), and the median duration of sustained MR4 before TKI discontinuation was 76.5 mo (range, 1.37-215.1). With a median follow-up of 66.8 mo (range, 4.7-211.4) after TKI discontinuation, 93 pts (26.5%) lost MMR after a median of 7.2 mo (range, 1.2-124.9) from stopping therapy. 88 (93%) pts regained MMR after resuming therapy after a median of 3.6 mo (range, 0.4-36.5). The median TFR duration was not reached, with a 5-year TFR rate of 72.2%. The 5-year TFR rates were 63.0% and 79.2% in pts with a MR4.5 duration of <5 years, and ≥5 years before cessation of the TKI, respectively. The 5-year TFR rates were 54.5%, and 80.4% in pts with a MR4 duration of <5 years, and ≥5 years before cessation of the TKI, respectively. There was no significant difference in the rates of 5-year TFR between pts who received frontline first- or second-generation TKIs (P=0.79). Five-year TFR rates were similar between pts who were treated at standard TKI dose and those treated with TKIs at reducing dosing (p=0.52). There was no significant difference in the TFR rates according to the BCR::ABL1 transcripts subtypes (p=0.1). Conclusions: The long-term follow-up results continue to demonstrate improved TFR rates of approximately 80% in patients who achieve a deep molecular response (MR4 or deeper response) sustained for 5 years or more.