Sequencing treatment in chronic myeloid leukemia: the first choice may be the hardest

Columbia University -Medical Center, New York, New York. The advent of tyrosine kinase inhibitors (TKIs) as primary treatment in chronic myeloid leukemia (CML) has greatly changed expectations of both physicians and patients. The use of imatinib has led not only to reliable cytogenetic responses, but also to deeper "molecular" responses that have brought long-term survival to a disease that was generally lethal in patients who were not candidates for stem cell transplantation. The more recent entrée of second-generation TKIs-nilotinib, dasatinib, bosutinib, and ponatinib-as well as the protein synthesis inhibitor omacetaxine, has provided access to more potent agents. These new drugs provide a safety net for patients whose disease does not respond to imatinib, but also create dilemmas for physicians treating CML patients. This review examines the evidence that informs choice of initial therapy, and discusses management options in the context of new goals of care, emerging toxicities, and the possibility of discontinuing treatment.