Risk Factors and Management of Patients with Pulmonary Abnormalities and Philadelphia Chromosome–Positive Leukemia After Treatment with Dasatinib: Results from Two Institutions

Abstract

Background

Dasatinib is a potent inhibitor of multiple tyrosine kinases, including Bcr-Abl and Src. Pleural effusions have occurred at an incidence of 21% in phase II studies with dasatinib. We investigated the incidence, clinical course, and management of pulmonary abnormalities in patients receiving dasatinib from 2 Canadian institutions.

Patients and Methods

Between March 2005 and November 2006, 38 patients with Philadelphia chomoseome–positive (Ph⁺) leukemia (chronic myeloid leukemia, n = 36; Ph⁺ acute lymphoblastic leukemia, n = 2) received dasatinib for imatinib resistance (n = 31) or intolerance (n = 7), 35 of whom received a 70-mg twice-daily regimen.

Results

With a median duration of 95 weeks of administration, 17 patients (45%) experienced pulmonary abnormalities, including 16 cases of pleural effusion (grade 1, n = 1; grade 2, n = 11; grade 3, n = 4) and 1 case of a lung parenchyma change (grade 3), with a median time to onset of 4 weeks after start of dasatinib. In total, 51 events were observed. The incidence of pulmonary abnormalities was higher in patients with a history of previous pulmonary disease and imatinib intolerance. Dasatinib therapy was temporarily interrupted in 16 patients, and resolution of the pulmonary abnormalities was evident within 4 weeks. Recurrences occurred within 13 weeks of dasatinib being reinitiated at a lower dose, with a median of 4 recurrence episodes. The development of these pulmonary abnormalities did not adversely affect patient responses to dasatinib.

Conclusion

We conclude that such pulmonary abnormalities are relatively common in patients receiving dasatinib and can have a late presentation (up to 21 months). Temporary dasatinib interruption is the best management strategy once they are recognized. Patients with pulmonary comorbidities and patients intolerant to previous imatinib therapy need to be carefully monitored for the occurrence of these abnormalities during dasatinib therapy.