Reducing the dosage of dasatinib does not prevent a second occurrence of fluid build-up in the lungs

This study examined a side effect called pleural effusion (PE; fluid build-up in the lungs) in patients with chronic myeloid leukemia (CML) treated with dasatinib (Sprycel). PE occurred in 23% of patients. This study concluded that reducing the dose of dasatinib after the first occurrence of PE did not prevent a recurrence. 

Targeted therapy is the standard first-line treatment for CML. This refers to a type of treatment that uses drugs or small molecules that block the growth and spread of cancer. Tyrosine kinase inhibitors are a type of targeted therapy. These block enzymes called tyrosine kinases. Dasatinib is a recently developed tyrosine kinase inhibitor approved for the first- and second-line treatment of CML.

Pleural effusion (PE) is a condition in which excess fluid builds around the lung. PE is a common side effect of dasatinib. The most common symptoms are dry cough, fatigue, decreased exercise tolerance, chest pain, and shortness of breath. While PE does not impact the effectiveness of dasatinib, it can lead to complications. 

The aim of this study was to look at strategies to reduce the recurrence of PE.

The records of 853 dasatinib-treated CML patients were analyzed. Most patients (82.6%) were treated with dasatinib as a second- or third-line therapy. Dasatinib starting dose was 100 mg/day in 70.4% of patients. 14.3% of patients received dasatinib at less than 100 mg/day. 15.3% of patients received dasatinib at more than 100 mg/day. Patients were followed for an average of 7.9 years.

23% of patients developed PE during treatment with dasatinib. The average time until PE developed was 16.6 months. 73.5% of PE cases occurred within the first 3 years. Most cases of PE were moderate to mild. No severe cases were observed.

At the time of first PE, 28.6% of patients were in major molecular response (a reduction in genetic abnormalities in the blood). 37.8% of patients were in deep molecular response (no evidence of genetic abnormalities in the blood).

29.1% of PE cases led to a discontinuation of dasatinib. Dasatinib was temporary interrupted in 71.9% of patients showing PE. Of these, 59.2% received a dose reduction when dasatinib was resumed. PE recurred in 59.4% of cases following treatment interruption. Among patients whose dosage was reduced, 59.5% experienced PE recurrence.

Most cases of PE were managed with diuretics (86.7%), followed by steroids (74.5%). 15.3% needed a procedure where fluid is drained from the lung. 

This study concluded that dasatinib dose reduction after the first episode of PE did not prevent PE recurrence. The authors suggested that once major or deep molecular response is achieved, the development of PE may be prevented by daily dose reductions or treatment-free weekends. However, future studies are needed to test this approach.

Further studies that randomly assign patients to different strategies to reduce PE are needed.