Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ adverse effects
Arterial Occlusive Diseases
/ chemically induced
Female
Humans
Imidazoles
/ adverse effects
Incidence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Male
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Protein Kinase Inhibitors
/ adverse effects
Pyridazines
/ adverse effects
Retrospective Studies
Young Adult
Acute lymphoblastic leukemia
Chronic myeloid leukemia
Safety
Tyrosine kinase inhibitor
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
06 01 2022
06 01 2022
Historique:
received:
21
09
2021
accepted:
18
12
2021
entrez:
7
1
2022
pubmed:
8
1
2022
medline:
16
2
2022
Statut:
epublish
Résumé
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. 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. 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. 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 ).
Sections du résumé
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 ).
Identifiants
pubmed: 34991679
doi: 10.1186/s13045-021-01221-z
pii: 10.1186/s13045-021-01221-z
pmc: PMC8734305
doi:
Substances chimiques
Antineoplastic Agents
0
Imidazoles
0
Protein Kinase Inhibitors
0
Pyridazines
0
ponatinib
4340891KFS
Banques de données
ClinicalTrials.gov
['NCT01207440']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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