title: Causes of resistance and treatment choices of second- and third-line treatment in chronic myelogenous leukemia patients.
abstract: For patients with chronic myelogenous leukemia who fail first-line therapy, several factors should be considered for the decision of the next treatment option. Second-generation tyrosine kinase inhibitors (TKIs) dasatinib, nilotinib, and bosutinib offer improved potency and a high likelihood of success for these patients. Overall, efficacy data are comparable for these agents, and so physicians should consider the BCR-ABL1 mutation profile and the patient's history to make a decision on the best choice. Only a few BCR-ABL1 mutations seem to be less responsive to any of the three drugs, and it is recommended to choose the second-line TKI that has shown clinical activity against the specific mutation in these cases. For patients with all other mutations and for patients with no mutations, it is recommended to choose the second-generation TKI based on the patient's disease history. The third-generation TKI ponatinib is available after dasatinib or nilotinib failure or for patients with T315I mutations. However, optimal dose of ponatinib is still under investigation. Overall, it is recommended to select a drug that minimizes the likelihood of worsening the patient's past side effects or comorbid conditions. In any case, chance and risk of allogeneic stem cell transplantation should be compared with the long-term outcome of TKI therapy in patients eligible for this procedure.
authors: Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Germany, andreas.hochhaus@med.uni-jena.de.
authors: Andreas
authors: A
authors: Hochhaus
authors: Thomas
authors: T
authors: Ernst
authors: Ekkehard
authors: E
authors: Eigendorff
authors: Paul
authors: P
authors: La Rosée
mesh_terms: D000814:Aniline Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069439:Dasatinib; D018450:Disease Progression; D016903:Drug Monitoring; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009154:Mutation; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D007093:Imidazoles; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D011743:Pyrimidines; D011804:Quinolines; D013844:Thiazoles; C545373:ponatinib; C471992:bosutinib; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib