Pleural Effusions More Common Than Previously Thought in Dasatinib-Treated Leukemias
With newer treatments, alternatives to dasatinib exist, if needed.
Between one-quarter and one-third of patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) treated with the tyrosine kinase inhibitor (TKI) dasatinib may experience drug-related pleural effusion, according to a recent study.1
Previous research has shown associations between fluid retention and other TKIs, but pleural effusions were more commonly reported with dasatinib.2,3
Timothy Hughes, MD, of University of Adelaide, Australia, and colleagues assessed dasatinib-related pleural effusion from the data in 2 phase 3 trials (DASISION and CA180-034) and a pooled population from 11 trials that used dasatinib to treat patients with CML or Philadelphia-positive ALL (DASISION and CA180-034 were analyzed separately and as part of the pooled population for this study).
Pleural effusion developed in between 6% to 9% of patients each year in the DASISION trial (258 patients), and between 5% to 15% of patients per year in the CA180-034 trial (662 participants). With a minimum of 5 years of follow-up, 28% of patients in DASISION reported drug-related pleural effusion, with most being grade 1 or grade 2. With a minimal follow-up of 7 years, drug-related pleural effusion occurred in 33% of patients in the CA180-034 trial; most incidences were grade 1 or grade 2. Among the pooled population of patients with Philadelphia-positive leukemia, drug-related pleural effusion of any grade occurred in approximately one-third of patients.
Overall responses to dasatinib and survival outcomes were similar between patients who had pleural effusion and those who did not. Multivariable analyses revealed a significant risk factor for developing pleural effusion was age. In DASISION, the median age of patients who developed drug-related pleural effusion was 56 years, but was 46 years in patients who did not experience pleural effusion. Similarly, in CA180-034, the median age at which patients developed pleural effusion was 60 years, but was 53 years in patients who did not.
There was no association found between pleural effusion and race, sex, region, exposure to interferon, BCR-ABL1 levels at 3 months, lymphocytosis, colitis, history of autoimmune disease, history of lung disease, history of skin rash, baseline smoking history, major molecular response at 12 months, average daily dose, line of therapy, baseline Euro risk scores, and duration of prior treatment with TKI therapy. In addition, Hughes and colleagues did not find that the dasatinib dose was a risk factor for development of pleural effusion in the pooled patient population.