Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: Data from the FDA Adverse Event Reporting System

Jorge Cortes, Michael Mauro, Juan Luis Steegmann, Giuseppe Saglio, Rachpal Malhotra, Jon A. Ukropec, Nicola T. Wallis

Research output: Contribution to journalArticle

Abstract

Rare but serious cardiovascular and pulmonary adverse events (AEs) have been reported in patients with chronic myeloid leukemia treated with BCR-ABL inhibitors. Clinical trial data may not reflect the full AE profile of BCR-ABL inhibitors because of stringent study entry criteria, relatively small sample size, and limited duration of follow-up. To determine the utility of the FDA AE Reporting System (FAERS) surveillance database for identifying AEs possibly associated with the BCR-ABL inhibitors imatinib, dasatinib, and nilotinib in the postmarketing patient population, we conducted Multi-Item Gamma Poisson Shrinker disproportionality analyses of FAERS reports on AEs in relevant system organ classes. Signals consistent with the known safety profiles of these agents as well as signals for less well-described AEs were detected. Bone marrow necrosis, conjunctival hemorrhage, and peritoneal fluid retention events were uniquely associated with imatinib. AEs that most commonly reached the threshold for dasatinib consisted of terms relating to hemorrhage and fluid retention, including pleural effusion and pericardial effusion. Most terms that reached the threshold solely with nilotinib were related to peripheral and cardiac vascular events. Although this type of analysis cannot determine AE incidence or establish causality, these findings elucidate the AEs reported in patients treated with BCR-ABL inhibitors across multiple clinical trials and in the community setting for all approved and nonapproved indications, suggesting drug-AE associations warrant further investigation. These findings emphasize the need to consider patient comorbidities when selecting amongst BCR-ABL inhibitors.

Original languageEnglish (US)
Pages (from-to)E66-E72
JournalAmerican Journal of Hematology
Volume90
Issue number4
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Lung
Clinical Trials
Hemorrhage
Osteonecrosis
Pericardial Effusion
Ascitic Fluid
Pleural Effusion
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Drug-Related Side Effects and Adverse Reactions
Causality
Sample Size
Blood Vessels
Comorbidity
Bone Marrow
Databases
Safety
Incidence
Population
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate

ASJC Scopus subject areas

  • Hematology

Cite this

Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors : Data from the FDA Adverse Event Reporting System. / Cortes, Jorge; Mauro, Michael; Steegmann, Juan Luis; Saglio, Giuseppe; Malhotra, Rachpal; Ukropec, Jon A.; Wallis, Nicola T.

In: American Journal of Hematology, Vol. 90, No. 4, 01.04.2015, p. E66-E72.

Research output: Contribution to journalArticle

Cortes, Jorge ; Mauro, Michael ; Steegmann, Juan Luis ; Saglio, Giuseppe ; Malhotra, Rachpal ; Ukropec, Jon A. ; Wallis, Nicola T. / Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors : Data from the FDA Adverse Event Reporting System. In: American Journal of Hematology. 2015 ; Vol. 90, No. 4. pp. E66-E72.
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