Dasatinib: efficacy, side effects and role of comorbidities

Abstract

Background and aim: Dasatinib, a dual Abl/Src tyrosine kinase inhibitor, has shown good efficacy in Chronic Myeloid Leukemia treatment, obtaining earlier and deeper response compared to Imatinib, in second and first line. The safety profile of Dasatinib was shown to be acceptable and manageable. In view of the very good clinical results, the issue of baseline comorbidities and their influence on promoting adverse events became relevant. Materials and methods: Both second and first line Dasatinib trials showed good efficacy with low toxicity. The most frequent side effects were thrombocytopenia, mainly observed during the first months of treatment, and pleural effusion. Results: The majority of side effects were of low grade and manageable with dose adjustments. The pleural effusion rate was 24% at 5-years. It was generally mild to moderate, reversible, manageable; only 5% of pts discontinued treatment due to PE. The median time of appearance is 40 weeks and most of them do not recur. The occurrence of pleural effusion generally do not affect the efficacy of Dasatinib. In the last years the role of comorbidities has been underlined as alert signal to prevent the occurrence of side effects by TKIs. Conclusion: A careful work up at diagnosis and during the treatment, other than to implement, in some cases, supportive therapy, would help to prevent the side effects, without neglecting the role of comorbidity that could be not considered as an absolute contraindication to treatment but a warning factor to take in account in the treatment choice.