Efficacy and safety of tyrosine kinase inhibitors in elderly patients with chronic myelogenous leukemia

Abstract

In patients with chronic myelogenous leukemia (CML), age is an important prognostic factor. According to registry data, 50% of patients with CML is ≥ 66 years old at the time of the diagnosis. Introduction of tyrosine kinase inhibitors (TKI) to CML treatment significantly changes the prognosis in this cohort of patients. Results of clinical trials performed in CML patients > 60 years confirmed clinical efficacy of imatinib (IM) similar to that observed in younger patients (complete cytogenetic response rates 79 v. 87%, respectively). However, in older patients the long-term disease outcome was worse (higher progression and death rates, event free survival, failure free survival, progression free survival, and overall survival). Also, IM treatment toxicity is higher. Moreover, discontinuation/temporary withdrawal of drug administration is more frequent. 2nd generation TKI (dasatinib, nilotinib) evaluation in the population of older patients confirmed their efficacy to be higher than IM in the 1st line of the treatment. Drugs were also effective in significant part of the patients with imatinib therapy intolerance/failure. The frequency of hematological toxicity, pleural and pericardial effusions (dasatinib) or rise in lipase activity and glucose concentration (nilotinib) and their clinical significance in elderly patients should be further investigated. It should be also remembered that poor adherence (compliance) is also an important factor influencing the results of the treatment.