Background: PON is a potent, multitargeted tyrosine kinase inhibitor with proven efficacy in resistant Ph+ leukemia. This analysis reports elevated BP and AEs of HTN in PON leukemia trials. Methods: PON safety and efficacy were evaluated in patients (pts) with relapsed/refractory hematologic malignancies in the ongoing phase (ph) 1 trial, in heavily pretreated CML/Ph+ ALL pts in the ongoing PACE (ph 2) trial, and in newly diagnosed CP-CML pts in the terminated EPIC (ph 3) trial vs imatinib (IM). Ph 1 and EPIC, but not PACE, excluded pts with uncontrolled HTN (untreated systolic/diastolic >150/>100 mm Hg in ph 1, > 140/> 90 mm Hg in EPIC). Elevated BP was defined by single highest measurement (systolic/diastolic): grade (G) 1/pre-HTN 120–139/80–89, G2 140–159/90–99, G3 ≥ 160/≥ 100 mm Hg. HTN AEs were reported by investigators. Results: Elevated BP was frequent at trial entry; G1/G2–3 rates: 44%/42% in ph 1; 37%/47% in PACE; 51%/19% PON vs 52%/12% IM in EPIC. Any increase in BP grade from baseline was also frequent: 74% in ph 1; 68% in PACE; 68% PON vs 51% IM in EPIC. In PACE, estimated systolic/diastolic BP increases over time were low: 2.3/0.7 mm Hg/year. HTN AEs were reported in 38%, 28%, 18%, and 2% of ph 1, PACE, EPIC-PON, and EPIC-IM pts, respectively. Hypertensive crisis was reported in 2 PACE and 2 EPIC-PON pts. HTN AEs did not lead to discontinuation or death. Few pts had dose modifications for HTN AEs (0% ph1; 5% PACE; 3% EPIC-PON; 0% EPIC-IM). A retrospective multivariate analysis of pooled pts showed HTN AEs were significantly associated with PON dose intensity. Conclusions: Increase in BP was frequently observed in PON trials, including in pts on IM. Rates of HTN AEs were relatively lower and seen primarily with PON. While associated with PON dose intensity, HTN AEs rarely led to change in therapy. Given BP variability, AE reporting may be a more reliable indicator of clinically meaningful HTN. Clinical trial information: NCT00660920; NCT01207440; NCT01650805

*Single measurement; Normal: <120/<80 mm Hg