Treatment-free remission in patients with chronic myeloid leukemia following the second discontinuation of tyrosine kinase inhibitors

Abstract Introduction Tyrosine kinase inhibitors (TKIs) discontinuation has been considered for chronic myeloid leukemia (CML) patients with deep molecular response (DMR). Approximately half of patients with TKI discontinuation experience molecular relapse (MRec). MRec following TKI withdrawal typically resolves with TKI reinitiation, and re-achievement DMR is a rationale for second treatment-free remission (TFR2). Method A retrospective study from 3 institutions was performed in 39 patients with a second TKI discontinuation. The candidates for first treatment-free remission (TFR1) had received TKI at least 4 years and achieved MR4.0 no less than 2 years. Results The median duration of MR4.0 before first TKI discontinuation was 52 months (26-137). Treatment before first discontinuation was imatinib in 58.9% (n=23), nilotinib in 30.8% (n=12), and dasatinib in 10.3% (n=4). The median time to MRec after the first TKI discontinuation was 5 months (1-42) and the median time from the first MRec to regaining MR4 was 4 months (1-12). After a median follow-up of 29 months (4-75) from the second TKI discontinuation, 33.3% (n=13) had re-initiated TKI therapy due to MRec. The median time to MRec was 5 months (2-19). Within the first 6-month and 12-month periods, MRec rates were 20.5% (n=8) and 37.8% (n=12), respectively. The median time to MR4.0 re-achievement was 3.5 months (2-8). In multivariate analyses, first MRec more than 4 months and duration of first MR4.0 more than 55 months were significant predictors of successful TFR2 (OR 0.043, 95% CI: 0.003-0.611; OR 0.016, 95% CI: 0.001-0.463). All 39 patients were alive at the final follow-up. Conclusion These results demonstrate that a second TKI stop is feasible and the majority of patients regain DMR within 6 months. Keywords: Chronic myeloid leukemia, Second, TKI discontinuation