Ponatinib in the PACE Phase II Trial: Response Data in Resistant CML and Ph+ ALL

　　PACE was an international,multicenter,open-label,single-arm phase II study of 449 patients with chronic-phase,accelerated-phase,or blast-phase CML,or Philadelphia chromosome–positive acute lymphoblastic leukemia(Ph+ALL).Most had resistance or intolerance to dasatinib or nilotinib,or carried the BCR-ABL1 T315I mutation.The starting dose was ponatinib 45 mg once daily,with hematologic,cytogenetic,and molecular responses assessed by disease stage.

　　Chronic-phase CML provided the strongest evidence.Among 267 evaluable patients,the 12-month major cytogenetic response(MCyR)rate was 56%,complete cytogenetic response(CCyR)46%,and major molecular response(MMR)34%.In the T315I subgroup,MCyR reached 70%,compared with 51%in patients resistant or intolerant to dasatinib or nilotinib—supporting activity against mutations that earlier BCR-ABL inhibitors often fail to control.

　　Responses declined as disease advanced.In accelerated-phase CML,the 6-month major hematologic response was 55%and MCyR 39%;in blast-phase CML these fell to 31%and 23%.Among 32 Ph+ALL patients,major hematologic response was 41%,MCyR 47%,and CCyR 38%,though the small subgroup warrants cautious interpretation alongside later studies and clinical context.

　　Five-year follow-up showed MCyR rising to 60%and MMR to 40%in chronic-phase CML,with an estimated 82%of MCyR responders maintaining that response at five years.Beyond efficacy,arterial occlusive events,hypertension,pancreatitis,and liver function abnormalities require close monitoring;arterial vascular events were also observed in PACE,so dosing should be balanced against both response and tolerability.

　　Taken together,PACE established ponatinib as a meaningful option after multiple lines of failure and in T315I-mutated disease.The clear gradient across disease stages,however,means chronic-phase results should not be extrapolated to blast-phase CML or Ph+ALL.