Clinical features of pulmonary arterial hypertension in patients receiving dasatinib.
The prognosis of most leukemia patients treated with BCR-ABL tyrosine kinase inhibitors (TKIs) is favorable, and a more precise understanding of serious and potentially irreversible treatment-related toxicities is essential to properly inform treatment choice. Few cases of pulmonary arterial hypertension (PAH) have been reported in patients with leukemia treated with dasatinib, a second-generation BCR-ABL TKI. To better understand characteristics and outcomes of dasatinib-treated patients with PAH, all clinical cases of PAH confirmed by right-heart catheterization in the Bristol-Myers Squibb pharmacovigilance database (N = 41), including 22 previously unpublished cases, were examined for previous treatments for leukemia, patient characteristics, time to PAH onset, and outcomes. Our analysis shows that compared with PAH due to other etiologies, dasatinib-related PAH is atypical, in that it is associated with partial to complete reversibility upon treatment discontinuation. The incidence of dasatinib-related PAH appears to be low. Most PAH cases were observed in patients who had received prior treatments for leukemia. No specific patient attributes appear to be associated with an increased risk of developing PAH while receiving dasatinib. Symptoms of PAH in dasatinib-treated leukemia patients should prompt a thorough workup, including consideration of confirmatory right-heart catheterization. In cases of confirmed PAH, dasatinib should be discontinued.
Division of Hematology/Oncology, San Francisco School of Medicine, University of California, San Francisco, California.
Neil P
NP
Shah
Department of Pulmonary Medicine, Critical Care and Allergy, Bristol-Myers Squibb, Princeton, New Jersey.
Nicola
N
Wallis
Boston University School of Medicine, Boston, Massachusetts.
Harrison W
HW
Farber
Memorial Sloan Kettering Cancer Center, New York, New York.
Michael J
MJ
Mauro
Department of Pulmonary Medicine, Critical Care and Allergy, Bristol-Myers Squibb, Princeton, New Jersey.
Robert A
RA
Wolf
Santa Croce Hospital, Cuneo, Italy.
Daniele
D
Mattei
Department of Pulmonary Medicine, Critical Care and Allergy, Bristol-Myers Squibb, Princeton, New Jersey.
Mausumee
M
Guha
Hôpital Saint-Louis, Paris, France.
Delphine
D
Rea
Scottish Pulmonary Vascular Unit, Glasgow, United Kingdom.
Andrew
A
Peacock
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006328:Cardiac Catheterization; D000069439:Dasatinib / Q000008:administration & dosage* / Q000009:adverse effects; D016208:Databases, Factual; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000175:diagnosis* / Q000503:physiopathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069439:Dasatinib