title: Considering baseline factors and early response rates to optimize therapy for chronic myeloid leukemia in chronic phase.
abstract: Multiple BCR-ABL tyrosine kinase inhibitors (TKIs) are available for the treatment of chronic myeloid leukemia in chronic phase (CML-CP), and several baseline and on-treatment predictive factors have been identified that can be used to help guide TKI selection for individual patients. In particular, early molecular response (EMR; BCR-ABL ≤10% on the International Scale at 3 months) has become an accepted benchmark for evaluating whether patients with CML-CP are responding optimally to frontline TKI therapy. Failure to achieve EMR is considered an inadequate initial response according to the National Comprehensive Cancer Network guidelines and a warning response according to the European LeukemiaNet recommendations. Here we review data supporting the importance of achieving EMR for improving patients' long-term outcomes and discuss key considerations for selecting a frontline TKI in light of these data. Because a higher proportion of patients achieve EMR with second-generation TKIs such as nilotinib and dasatinib than with imatinib, these TKIs may be preferable for many patients, particularly those with known negative prognostic factors at baseline. We also discuss other considerations for frontline TKI choice, including toxicities, cost-effectiveness, and the emerging goals of deep molecular response and treatment-free remission.
authors.affiliation: a Indiana Blood and Marrow Transplantation, Franciscan St Francis Hospital and Health Centers , Indianapolis , IN , USA ;
authors.forename: Luke P
authors.initials: LP
authors.lastname: Akard
authors.affiliation: b Division of Hematology and Oncology, Department of Internal Medicine , University of Michigan Comprehensive Cancer Center , Ann Arbor , MI , USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Bixby
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D057915:Drug Substitution; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D058990:Molecular Targeted Therapy; D017410:Practice Guidelines as Topic; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019233:Retreatment; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL; chronic myeloid leukemia; early molecular response; tyrosine kinase inhibitors