Dasatinib Related Pleural Effusions: Real-World Experience in a District General Hospital

ABSTRACT

Dasatinib, a second-generation BCRABL1 tyrosine kinase inhibitor (TKI), is an approved treatment for chronic myeloid leukaemia, both as first-line therapy and following imatinib intolerance or resistance. It is generally well tolerated, however, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors and outcomes of this significant side effect were analysed in the phase 3 DASISION and 034/Dose-optimization trials. Annual risk of 5%-15% was reported. Drug-related pleural effusion occurred in 28%-33% of patients in a minimum of 5-year follow-up period. One major risk factor was advanced age. We therefore reviewed a cohort of 34 patients treated with dasatinib between 2016 and 2021, to determine 'real-world' data of this toxicity. Case notes, pathology results and radiological reports were analysed. We identified 12 (35%) cases of pleural effusions. Eight (66%) cases were male. The median average age of patients with and without drug-related pleural effusion were 59.5 years (range 31-91 years) and 54.5 years (range 20-88 years) respectively. Cardiovascular and respiratory comorbidities were noted in eight patients (66.6%) with pleural effusion (ischaemic heart disease, hypertension, lung cancer, COVID, peripheral vascular disease and hyperlipidaemia) and nine patients (41%) without pleural effusion (prior non-TKI pleural effusion, hypertension, asthma, congenital heart defect, COPD and atrial fibrillation). Nine cases (75%) of those with pleural effusion were non-smokers. Lymphocytosis was not noted in any of those 12 cases of drug-related pleural effusion. Ten cases (83%) were on dasatinib 100 mg daily when pleural effusion was diagnosed, one was on 50 mg daily and the other was on 20 mg daily. Pleural effusion occurred after a median of 36 months (range 6-108 months). Nine cases (75%) were mild to moderate in severity-Common Terminology Criteria for Adverse Events (CTCAE ) grade 1-2, two were grade 3 and one was grade 4. Two required no intervention, three required only medical intervention (steroid+/-antibiotics), three required pleural tap and three required pleural drain. One required VATS procedure with talc pleurodesis. The patient with grade 1 pleural effusion required no treatment change. One required dose reduction of dasatinib without interruption. One required temporary interruption but restarted on the same dose. Six required temporary interruption of dasatinib followed by dose reduction to 50 mg daily. Two of these subsequently recurred on lower dose dasatinib and were then switched to an alternative TKI (bosutinib and imatinib). Two required temporary TKI interruption and were restarted on a different TKI (nilotinib). One case of pleural effusion persisted and the patient was kept off TKI treatment. Although the numbers are too small for statistically robust analysis, we have observed several trends which may help to guide patient counselling and selection. Pleural effusion has an incidence of 35% in our local population. Risk factors were cardiovascular and respiratory comorbidities, advanced age and male sex. Smoking status and lymphocytosis did not appear to be risk factors in our cohort, where they have been in other reports. Most effusions were mild to moderate in severity and could usually be managed by steroid+/-pleural tap+/-drain. Most patients required temporary interruption of their dasatinib but were successfully able to restart at a lower dose without recurrence..