Tailoring tyrosine kinase inhibitor therapy to tackle specific BCR-ABL1 mutant clones.
Several tyrosine kinase inhibitors (TKIs) are currently under development for the treatment of patients with chronic myelogenous leukemia (CML) resistant or intolerant of imatinib therapy, including nilotinib, dasatinib, and bosutinib. The current paradigm of TKI therapy involves a sequential use of these compounds, with imatinib invariably used as frontline therapy followed by either dasatinib or nilotinib on an empiric basis. A more sensible approach to this sequence is the selection of the TKI best suited to overcome the resistance conferred by BCR-ABL1 mutations detected at each time-point. As more TKIs are becoming available, the management of patients with CML will require degree of "finesse" to better match each patient with the best TKI available. This match is best made based on available in vitro data regarding the activity of each agent against each specific mutation. The case herein reported supports such strategy.
Quintás-Cardama
Alfonso
A
Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Unit 428, Houston, TX 77030, USA. aquintas@mdanderson.org
Cortes
Jorge
J
D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate