title: Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: A systematic review and a meta-analysis.
abstract: Tyrosine kinase inhibitors (TKIs) are the cornerstones of treatment for patients with chronic myeloid leukaemia (CML). In recent years, several studies were conducted to evaluate the safety of TKIs discontinuation. We performed a systematic review of the literature to determine the incidence of CML relapse, to identify possible factors relapse rates and to evaluate the long-term safety in CML patients with stable undetectable BCR-ABL transcript level who discontinued TKIs.
  
  
  
  Studies evaluating TKIs discontinuation in CML patients with undetectable BCR-ABL transcript level were identified by electronic search of MEDLINE and EMBASE database until May 2015. Weighted mean proportion and 95% confidence intervals (CIs) of CML relapse was calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2statistic.
  
  
  
  Fifteen cohort studies, for a total of 509 patients, were included. Nine studies were at low-risk of bias. All 15 studies included only patients on imatinib. Overall weighted mean molecular relapse rate of CML was 51% (95% CI 44-58%; I2= 55). Weighted mean molecular relapse rate at 6-month follow-up was 41% (95% CI 32-51%; I2= 78). Eighty percent of molecular relapses occurred in the first 6 months. All 509 patients were alive at 2-year follow-up and only one patient (0.8%, 95% CI 0.2-1.8%; I2= 0) has progressed to a blastic crisis.
  
  
  
  Our findings suggest that imatinib discontinuation is feasible for the majority of CML patients with stable undetectable BCR-ABL transcript level. Approximately 50% of patients remain therapy-free after imatinib discontinuation. Restarting TKIs therapy was followed by a very high rate of molecular response, with no deaths 2 years after discontinuation.
authors.affiliation: Department of Medicine and Surgery, University of Insubria, Varese, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Campiotti
authors.affiliation: Department of Medical Oncology, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
authors.forename: Matteo Basilio
authors.initials: MB
authors.lastname: Suter
authors.affiliation: Department of Medicine and Surgery, University of Insubria, Varese, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.affiliation: Hematology and Clinical Research Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Piazza
authors.affiliation: Hematology and Clinical Research Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti-Passerini
authors.affiliation: Department of Medicine and Surgery, University of Insubria, Varese, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Grandi
authors.affiliation: Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address: alessandro.squizzato@uninsubria.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Squizzato
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D057915:Drug Substitution; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukaemia; Discontinuation; Imatinib; Review; Tyrosine-kinase inhibitors