Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee

James L. Januzzi, Joseph M. Garasic, Scott E. Kasner, Vickie McDonald, Mark C. Petrie, Jonathan Seltzer, Michael Mauro, Kevin Croce, Ellin Berman, Michael Deininger, Andreas Hochhaus, Javier Pinilla-Ibarz, Franck Nicolini, Dong Wook Kim, Daniel J. DeAngelo, Hagop Kantarjian, Jing Xu, Tracey Hall, Shouryadeep Srivastava, Daniel NaranjoJorge Cortes

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used. Methods: To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. Results: A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. Conclusions: This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 (https://clinicaltrials.gov/ct2/show/NCT01207440).

Original languageEnglish (US)
Article number1
JournalJournal of Hematology and Oncology
Volume15
Issue number1
DOIs
StatePublished - Dec 2022

Keywords

  • Acute lymphoblastic leukemia
  • Chronic myeloid leukemia
  • Safety
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

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