title: Discontinuing Tyrosine Kinase Inhibitor Therapy in Chronic Myelogenous Leukemia: Current Understanding and Future Directions.
abstract: BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically transformed the treatment of patients with chronic myelogenous leukemia (CML). Given the impressive and sustained response to TKI therapy that the majority of treated patients with CML enjoy, recent studies have explored the potential to achieve treatment-free remission in select patients, which may allow these patients to escape the adverse clinical and financial effects associated with life-long TKI therapy. The results of multiple prospective trials have demonstrated that patients who maintain a deep molecular response for at least 2 years with TKI treatment may be eligible for trial of TKI discontinuation. Mounting data indicates that approximately 40% of those who discontinue therapy on trial will remain in remission at least 1 year after TKI discontinuation; the majority of patients with molecular recurrence relapse within the first 6 months after TKI discontinuation, and TKI retreatment is highly effective in restoring response. Sokol score, duration of TKI therapy, depth of molecular response, and the presence of natural killer cells may all be associated with a higher probability of attaining treatment-free remission. Moving forward, emerging data from ongoing TKI discontinuation trials will allow for appropriate selection of patients with CML eligible for this approach, will expand our current understanding of the CML stem cell, and identify therapeutic interventions capable of effectively deleting the malignant hematopoietic stem cell.
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Sheena
authors.initials: S
authors.lastname: Bhalla
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Douglas
authors.initials: D
authors.lastname: Tremblay
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: John.mascarenhas@mssm.edu.
authors.forename: John
authors.initials: J
authors.lastname: Mascarenhas
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019468:Disease Management; D016903:Drug Monitoring; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy; D018365:Neoplasm, Residual / Q000175:diagnosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D017211:Treatment Failure; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: Cure; Dasatinib; Imatinib; Molecular remission; Nilotinib