title: Long-Term Side Effects of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.
abstract: Most patients with chronic myeloid leukemia have deep and durable responses when treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs). Imatinib (the first approved TKI), nilotinib, and dasatinib are used in newly diagnosed, relapsed or intolerant patients, while bosutinib and ponatinib are used only in relapsed or intolerant patients. Previously the drug of choice was related to the likelihood of response and, to a small extent, patient comorbidities. The long-term toxicities, particularly cardiopulmonary side effects, are now impacting treatment choice, making patient comorbidities of significant concern. About 10 % of patients do not tolerate their initial BCR-ABL1 TKI and an increasing number are developing long-term side effects, particularly with the second generation drugs. Side effects of the five drugs reviewed here highlight the differences between cardiovascular, pulmonary, gastrointestinal, and endocrine toxicities, as well as possible second malignancies. There is increasing evidence that patients whose disease is controlled by TKI's will have greater impact on their quality of life from comorbidities or drug adverse events than from the disease itself. Research into management of long-term toxicities is needed.
authors.affiliation: Indiana Blood and Marrow Transplantation, Franciscan Alliance, 8111 South Emerson Avenue Suite 207, Indianapolis, IN, 46237, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Caldemeyer
authors.affiliation: Indiana Blood and Marrow Transplantation, Franciscan Alliance, 8111 South Emerson Avenue Suite 207, Indianapolis, IN, 46237, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Dugan
authors.affiliation: Indiana Blood and Marrow Transplantation, Franciscan Alliance, 8111 South Emerson Avenue Suite 207, Indianapolis, IN, 46237, USA.
authors.forename: John
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Indiana Blood and Marrow Transplantation, Franciscan Alliance, 8111 South Emerson Avenue Suite 207, Indianapolis, IN, 46237, USA. lakard@ibmtindy.com.
authors.forename: Luke
authors.initials: L
authors.lastname: Akard
mesh_terms: D066126:Cardiotoxicity; D002986:Clinical Trials as Topic; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008171:Lung Diseases / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D047428:Protein Kinase Inhibitors
keywords: BCR-ABL1; CML; Dasatinib; Imatinib; Nilotinib; TKI