title: Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.
abstract: Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.
authors.affiliation: Hematology Unit, First Department of Internal Medicine, Laiko Hospital, University of Athens, 17 Agiou Thoma Street, Athens 11527, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Iliakis
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Papadopoulou
authors.forename: Panagiotis T
authors.initials: PT
authors.lastname: Diamantopoulos
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Panayiotidis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zervakis
authors.forename: Nefeli
authors.initials: N
authors.lastname: Giannakopoulou
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Tilimidos
authors.forename: Maria
authors.initials: M
authors.lastname: Angelopoulou
authors.forename: Marina P
authors.initials: MP
authors.lastname: Siakantaris
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Pangalis
authors.forename: Marina
authors.initials: M
authors.lastname: Mantzourani
authors.forename: Eleni
authors.initials: E
authors.lastname: Variami
authors.forename: Nora Athina
authors.initials: NA
authors.lastname: Viniou
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: Chronic-phase CML; TKI; complete molecular response