Background: PON, a potent oral TKI, is active against native and mutant BCR-ABL1 and approved for pts with refractory CML or Ph+ALL, or with the T315I mutation. Pt responses at early landmark time points have been correlated with positive long-term (LT) outcomes in 1st and 2nd-lines. Here we evaluate the impact of early responses with PON on 3-yr outcomes in heavily pretreated pts (primarily ≥3rd line) with CP-CML in the ongoing Ph2 PACE trial. Methods: Molecular and cytogenetic responses at 3, 6 and 12 mo and their association with outcomes at 3 yrs were examined among CP-CML (n=267) pts in a posthoc analysis. P values: calculated using log-rank test. Data: as of 3 Aug 2015. Results: Median time from diagnosis was 7 yrs (range 0.5-27) and median age was 60 yrs (range 18-94); 61% had received ≥3 prior TKIs. At 3, 6, and 12 mo, 48%, 62% and 71% of pts, respectively, achieved MCyR, and 14%, 29% and 39%, respectively, achieved MMR, among pts evaluable at each landmark. Greater reductions in BCR-ABL1 transcript levels at most landmark time points were associated with improved PFS and OS at 3 yrs (Table), as was MCyR. Deeper responses at all landmark time points were also associated with the achievement of MR4.5 over time. Conclusions: Deep, early reductions in BCR-ABL1 transcripts were positively associated with LT survival in this refractory population. These data demonstrate the prognostic value of achieving early landmark cytogenetic and molecular responses with PON in heavily pretreated pts. Clinical trial information: NCT01207440

*Calculated across the entire post-landmark timespan and unadjusted for multiple comparisons.