Safety profiles of first-line TKIS and managing adverse effects

The treatment armamentarium of chronic myeloid leukemia (CML) is based on at least five TKIs, employed either in first-line CP (imatinib, dasatinib, and nilotinib) and in second and third line (dasatinib, nilotinib, bosutinib, and ponatinib). These drugs share the same target of interest (BCR-ABL) but have profound different off-target effects. In turn, the general spectrum of adverse events experienced by the treated patients, either clinical symptoms, biochemical abnormalities, or severe AEs (or “complications”), varies considerably. SAEs are more frequent with second- and third-generation TKIs, and from this point of view, imatinib remains the safest drug. The early identification of CML patient candidates to experience more frequently SAEs with second (and third)-generation TKIs is of course part of the treatment decision process where the right balance between risk and benefit should be accomplished. Second-generation TKIs, nilotinib and dasatinib, are considered generally to be better tolerated than imatinib. However, two types of complications are described more frequently with nilotinib and ponatinib (cardiovascular, in general, and PAOD in particular) and with dasatinib (pleural effusions and pulmonary hypertension) if compared with imatinib. These two types of complications deserve a particular attention.