Management options for refractory chronic myeloid leukemia: considerations for the elderly

Despite the excellent results obtained with standard-dose imatinib as first-line therapy for chronic myeloid leukemia in the chronic phase, one third of patients do not achieve an optimal response and require alternative therapies due to the emergence of drug resistance. Studies of resistance mechanisms, first tested in vitro and then in vivo, have driven the development of second-generation tyrosine kinase inhibitors (TKIs), dasatinib and nilotinib. These agents have been proven effective in a large number of patients resistant to imatinib and are also effective in older patients. The use of second-generation TKIs in first-line treatment has increased the rate of cytogenetic and molecular responses and reduced the number of patients experiencing disease progression. In this review, we detail the various mechanisms of resistance and management options for refractory patients, in particular in older patients. No differences in terms of efficacy were reported in this subset of patients when treated with nilotinib or dasatinib after imatinib resistance. Results of trials that tested second-generation TKIs as first-line treatment showed similar results in older and younger patients.