Second attempt to discontinue TKI after molecular relapse in patients with chronic myeloid leukemia: A real‐life Italian multicenter study

Background: Approximately half of patients with chronic myeloid leukemia (CML) who attempted tyrosine kinase inhibitor (TKI) discontinuation for the first time experienced molecular relapse and restarted TKIs. Although several studies have already investigated first treatment-free remission (TFR) attempts (TFR1), few previously published articles have focused on the plausibility and predictors of second TFR (TFR2). Methods: To evaluate the feasibility and likelihood of TFR2 success in real-life, 90 patients with CML regularly followed in 23 Italian hematological centers were analyzed; these patients reattempted TKI discontinuation after a first failed attempt. Results: Forty-five (50.0%) patients lost major molecular response after a median of 4.0 months off therapy, whereas 45 (50.0%) remained treatment-free for a median of 18.8 months. In univariate analysis, there was no association between TFR2 and the following variables: age, gender, Sokal risk score, BCR::ABL1 transcript type, prior interferon exposure, type and number of previous TKIs, resistance to any prior TKIs, and TKI switching after TFR1. In contrast, factors identified as associated with TFR2 success included a lower ELTS risk score, a longer time from TFR1 to molecular relapse (≥3 months), as well as a longer TKI treatment and deep molecular response (DMR) duration (≥4 years) before TFR2. Conclusions: While confirming the critical prognostic role of ELTS risk and TKI treatment and DMR duration even before TFR2, this real-life study provides further information to support the safety of a second effort to discontinue TKIs in patients with CML, as a failed first attempt does not appear to preclude a second successful one.