PF408 DASFREE 2‐YEAR UPDATE: DASATINIB DISCONTINUATION IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML‐CP) AND DEEP MOLECULAR RESPONSE (DMR)
Authors: Shah N. , García‐Gutiérrez J.V. , Jiménez‐Velasco A. , Larson S. , Saussele S. , Rea D. , Mahon F.‐X. , Levy M.Y. , Gómez‐Casares M.T. , Luciano L. , Nicolini F.‐E. , Mauro M.J. , Sy O. , Martin‐Regueira P. , Lipton J.H. 
Published: June 2019

Background:Treatment‐free remission (TFR) is a potential treatment goal for pts with CML‐CP. Sustained TFR has previously been reported for pts enrolled in the DASFREE trial (CA180406/NCT01850004), in which a 48% rate of relapse‐free survival was observed at 18 mo after dasatinib discontinuation (Shah Blood 2018). Here we report results for pts in DASFREE with a minimum of 2 y of follow‐up.Aims:To assess the durability of TFR at 2 y after discontinuing dasatinib treatment in pts with CML‐CP and dasatinib‐induced DMR.Methods:DASFREE is an open‐label, single‐arm phase 2 study in adult pts with CML‐CP on first‐line (1L) or subsequent‐line (≥2L) dasatinib for ≥2 y and with DMR (MR4.5; BCR‐ABL1 ≤0.0032% on the International Scale [IS]). MR4.5 was confirmed at a local lab for ≥1 y prior to enrollment and confirmed at a central lab twice within 3 mo prior to dasatinib discontinuation. BCR‐ABL1 was monitored centrally every mo after discontinuation in the 1st y and every 3 mo thereafter. If major molecular response (MMR; BCR‐ABL1 ≤0.1% IS) was lost, pts resumed dasatinib at their previous dose. The primary endpoint was the rate of MMR at 12 mo after discontinuation without restarting dasatinib. Key secondary endpoints include event‐free survival (EFS; survival with no loss of MMR), rate of transformation to accelerated phase/blast crisis (AP/BC), progression‐free survival (PFS; survival without progression to AP/BC), and overall survival. Key exploratory analyses include the frequency of adverse events (AEs) on and off treatment.Results:Pt characteristics were previously reported; briefly, 37 pts (44%) discontinued 1L dasatinib and 47 pts (56%) discontinued ≥2L dasatinib (Shah Blood 2018). To date, 11 pts (13%) have discontinued the study (2 off‐treatment; 9 after restarting dasatinib). In total, 46 pts lost MMR (1 pt lost MMR at mo 39 and had not restarted therapy at the time of this analysis) after a median of 4 mo (range 1–39) after discontinuation. Of the 46 pts who lost MMR, 45 (98%) restarted on dasatinib; 44 of 45 (98%) regained MMR after a median of 2 mo (range 1–4) and 43 (96%) regained MR4.5 after a median of 3 mo (range 2–18) (Figure). At 2 y, EFS was 46% (95% confidence interval [CI] 36, 57) in all pts, 51% (95% CI 35, 67) in 1L pts, and 42% (95% CI 28, 57) in ≥2L pts. PFS at 2 y was 99% (95% CI 96, 100) in all pts (there was 1 death unrelated to CML). No pts transformed to AP/BC. Time on prior treatment (regardless of line of dasatinib) was 65 mo for pts who lost MMR (n = 19) and 73 mo for pts who maintained MMR (n = 18). A univariate analysis revealed statistically significant associations between EFS and older age (hazard ratio [HR] 2.722; 95% CI 1.126, 6.578; P = 0.0261) and prior 1L therapy (HR 0.381; 95% CI 0.162, 0.893; P = 0.0265). All AEs observed thus far in DASFREE have been consistent with the known safety profile of dasatinib. There were 2 additional withdrawal events (in the same pts) at this follow‐up.Summary/Conclusion:Extended follow‐up results from DASFREE continue to support the feasibility of TFR in pts with CML‐CP who achieve stable DMR with dasatinib. The observed durability of TFR at 2 y (with 46% of all pts maintaining EFS) provides clinically relevant information for many pts considering TFR with dasatinib in the 1L and beyond. Lastly, no new pts experienced withdrawal events.image