Background: Ponatinib is approved for pts with refractory CML or Ph+ ALL for whom no other TKI therapy is indicated, or for patients with T315I. Previously (Mueller ASCO ‘16), we reported the positive association of early landmark responses with ponatinib on survival at 3 yrs in heavily pretreated pts with CP-CML in PACE (NCT01207440). Here, we provide an update with survival outcomes at 4 yrs. Methods: The association of molecular (assessed in a central lab) and cytogenetic responses (CyR) at 3, 6 and 12 mo with 4-yr post-landmark PFS and OS was evaluated in CP-CML pts (n = 267). P values: calculated using log-rank test. Data cutoff: 3 Oct ‘16. Results: At baseline, median time from diagnosis: 7 (range, 0.5–27) yrs; median age: 60 (18–94) yrs; median %Ph+: 100% (3–100), ≤10% Ph+: 19 pts (7%); 61% of pts had ≥3 prior TKIs. Among evaluable pts at 3, 6 and 12 mo, MCyR/CCyR was achieved in 48%/39%, 62%/52% and 71%/56% and MMR in 14%, 29% and 39% of pts, respectively. Greater reductions in BCR-ABL1 levels (Table) and CyR at most landmark time points were associated with improved 4-yr post-landmark PFS and OS. Deeper responses at all landmark time points were associated with achievement of MR^4.5 over time. Conclusions: As with the 3-yr landmark analysis, CyR and deep reductions in BCR-ABL1 transcripts at early time points correlated with improved 4-yr post-landmark survival in this refractory population. These data continue to demonstrate the prognostic value of early cytogenetic and molecular responses with ponatinib in heavily pretreated pts with CP-CML. Clinical trial information: NCT01207440

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