Pleural effusions due to dasatinib

Abstract

Dasatinib is a novel tyrosine-kinase inhibitor approved for treatment of BCR-ABL positive chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) after imatinib failure. Use of dasatinib is frequently complicated by pleural effusions. This review highlights the risk factors for development of effusions as well as characteristics of the pleural fluid. Potential mechanisms involved and a set of management recommendations based on available evidence are also discussed. The incidence of dasatinib-associated pleural effusions is approximately 20%. A twice-daily dosing regimen was found to significantly correlate with development of effusions, and therefore once-daily dosing is now approved for treatment of chronic myeloid leukemia and acute lymphoblastic leukemia. Dasatinib-associated pleural effusions are generally lymphocyte-predominant exudates. The mechanism of occurrence is unknown but may involve an immune-mediated pathway or off-target inhibition of platelet-derived growth factor receptor, beta polypeptide. Management typically involves dose interruption or reduction, diuretics and short-term corticosteroid therapy. Dasatinib is a promising agent for the treatment of refractory chronic myeloid leukemia and acute lymphoblastic leukemia. Its use can be complicated by development of exudative pleural effusions of unclear etiology. Incidence is decreasing with once-daily dosing, but when effusions do occur, most can be managed with specific measures without necessitating discontinuation of therapy.