TY - JOUR
T1 - Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee
AU - Januzzi, James L.
AU - Garasic, Joseph M.
AU - Kasner, Scott E.
AU - McDonald, Vickie
AU - Petrie, Mark C.
AU - Seltzer, Jonathan
AU - Mauro, Michael
AU - Croce, Kevin
AU - Berman, Ellin
AU - Deininger, Michael
AU - Hochhaus, Andreas
AU - Pinilla-Ibarz, Javier
AU - Nicolini, Franck
AU - Kim, Dong Wook
AU - DeAngelo, Daniel J.
AU - Kantarjian, Hagop
AU - Xu, Jing
AU - Hall, Tracey
AU - Srivastava, Shouryadeep
AU - Naranjo, Daniel
AU - Cortes, Jorge
N1 - Funding Information:
We thank the patients, their families, and their caregivers, and the study investigators and their team members at each site for participation in the PACE trial. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Presented in part at Januzzi, J.L., Garasic, J., Kasner, S. et al. (2020). "An independent review of arterial occlusive events (AOEs) in the ponatinib (PON) phase II PACE trial (NCT01207440) in patients (pts) with Ph+ leukemia [abstract]." Journal of Clinical Oncology 38(15 suppl): 7550. Januzzi, J., Garasic, J., Kasner, S. et al. (2020). "Retrospective independent review of arterial occlusive events (AOES) in the phase 2 pace trial of ponatinib in Philadelphia chromosome-positive (PH+) leukemia [abstract]." HemaSphere 4(Suppl 1): 338; Januzzi, J., Garasic, J., Kasner, S. et al. (2020). "Retrospective independent review of arterial occlusive events in the phase 2 pace trial of ponatinib in Philadelphia chromosome-positive leukemia [abstract]." Presented at the 8th Annual Meeting (Virtual) of the Society of Hematologic Oncology (SOHO), September 9–12, 2020; Januzzi, J., Garasic, J., Kasner, S. et al. (2020). "Retrospective independent review of arterial occlusive events in the phase 2 pace trial (NCT01207440) of ponatinib in Philadelphia chromosome-positive leukemia [abstract]." Presented at the John Goldman E-Conference on Chronic Myeloid Leukemia: Biology and Therapy (iCMLf) October 1–4, 2020.xxx
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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).
AB - 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).
KW - Acute lymphoblastic leukemia
KW - Chronic myeloid leukemia
KW - Safety
KW - Tyrosine kinase inhibitor
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U2 - 10.1186/s13045-021-01221-z
DO - 10.1186/s13045-021-01221-z
M3 - Article
C2 - 34991679
AN - SCOPUS:85122504355
SN - 1756-8722
VL - 15
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 1
ER -
