Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients

David J. Dorer, Ronald K. Knickerbocker, Michele Baccarani, Jorge E. Cortes, Andreas Hochhaus, Moshe Talpaz, Frank G. Haluska

Research output: Contribution to journalArticle

Abstract

Ponatinib is approved for adults with refractory chronic myeloid leukemia or Philadelphia chromosome–positive acute lymphoblastic leukemia, including those with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N = 671) to determine the impact of ponatinib dose intensity on the following adverse events: arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular events), venous thromboembolic events, cardiac failure, thrombocytopenia, neutropenia, hypertension, pancreatitis, increased lipase, increased alanine aminotransferase, increased aspartate aminotransferase, rash, arthralgia, and hypertriglyceridemia. Multivariate analyses allowed adjustment for covariates potentially related to changes in dosing or an event. Logistic regression analysis identified significant associations between dose intensity and most events after adjusting for covariates. Pancreatitis, rash, and cardiac failure had the strongest associations with dose intensity (odds ratios >2). Time-to-event analyses showed significant associations between dose intensity and risk of arterial occlusive events and each subcategory. Further, these analyses suggested that a lag exists between a change in dose and the resulting change in event risk. No significant association between dose intensity and risk of venous thromboembolic events was evident. Collectively, these findings suggest a potential causal relationship between ponatinib dose and certain adverse events and support prospective investigations of approaches to lower average ponatinib dose intensity.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalLeukemia Research
Volume48
DOIs
StatePublished - Sep 1 2016

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Multivariate Analysis
Clinical Trials
Exanthema
Pancreatitis
Population
Heart Failure
Hypertriglyceridemia
Arthralgia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Aspartate Aminotransferases
Neutropenia
Lipase
Alanine Transaminase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Thrombocytopenia
Blood Vessels
Logistic Models
Odds Ratio
Regression Analysis
Hypertension

Keywords

  • BCR-ABL1
  • Chronic myeloid leukemia
  • Dose intensity
  • Philadelphia chromosome
  • Ponatinib
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Impact of dose intensity of ponatinib on selected adverse events : Multivariate analyses from a pooled population of clinical trial patients. / Dorer, David J.; Knickerbocker, Ronald K.; Baccarani, Michele; Cortes, Jorge E.; Hochhaus, Andreas; Talpaz, Moshe; Haluska, Frank G.

In: Leukemia Research, Vol. 48, 01.09.2016, p. 84-91.

Research output: Contribution to journalArticle

Dorer, David J. ; Knickerbocker, Ronald K. ; Baccarani, Michele ; Cortes, Jorge E. ; Hochhaus, Andreas ; Talpaz, Moshe ; Haluska, Frank G. / Impact of dose intensity of ponatinib on selected adverse events : Multivariate analyses from a pooled population of clinical trial patients. In: Leukemia Research. 2016 ; Vol. 48. pp. 84-91.
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