title: Impact of age on efficacy and toxicity of nilotinib in patients with chronic myeloid leukemia in chronic phase: ENEST1st subanalysis.
abstract: OBJECTIVE
  Achievement of deep molecular response with a tyrosine kinase inhibitor in patients with chronic myeloid leukemia (CML) is required to attempt discontinuation of therapy in these patients. The current subanalysis from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study evaluated whether age has an impact on the achievement of deeper molecular responses or safety with frontline nilotinib in patients with CML.
  
  
  METHODS
  ENEST1st is an open-label, multicenter, single-arm, prospective study of nilotinib 300 mg twice daily in patients with newly diagnosed CML in chronic phase. The patients were stratified into the following 4 groups based on age: young (18-39 years), middle age (40-59 years), elderly (60-74 years), and old (≥75 years). The primary end point was the rate of molecular response 4 ([MR4] BCR-ABL1 ≤0.01% on the international scale) at 18 months from the initiation of nilotinib.
  
  
  RESULTS
  Of the 1091 patients enrolled, 1089 were considered in the analysis, of whom, 23% (n = 243), 45% (n = 494), 27% (n = 300), and 5% (n = 52) were categorized as young, middle age, elderly, and old, respectively. At 18 months, the rates of MR4were 33.9% (95% confidence interval [CI], 27.8-40.0%) in the young, 39.6% (95% CI, 35.3-44.0%) in the middle-aged, 40.5% (95% CI, 34.8-46.1%) in the elderly, and 35.4% (95% CI, 21.9-48.9%) in the old patients. Although the incidence of adverse events was slightly different, no new specific safety signals were observed across the 4 age groups.
  
  
  CONCLUSIONS
  This subanalysis of the ENEST1st study showed that age did not have a relevant impact on the deep molecular response rates associated with nilotinib therapy in newly diagnosed patients with CML and eventually on the eligibility of the patients to attempt treatment discontinuation.
authors.affiliation: Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. frankgiles@aol.com.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, "Seràgnoli" Institute of Hematology, "S. Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nicholas C P
authors.initials: NCP
authors.lastname: Cross
authors.affiliation: Hematology Department, IIS-IP, Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Steegmann
authors.affiliation: Vilnius University Hospital Santariskiu Clinics, Vilnius University, Vilnius, Lithuania.
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
authors.affiliation: Charité - Universitätsmedizin Berlin Campus Virchow, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: Fundeni Clinical Institute, University of Medicine "Carol Davila" Bucharest, Bucharest, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Coriu
authors.affiliation: Ion Chiricuta Instititute of Oncology, Cluj-Napoca, Romania.
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Petrov
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.affiliation: Hematology Laboratory, Bordeaux University, Bordeaux, France.
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.affiliation: Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Saussele
authors.affiliation: Department of Hematology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology and Hematology Research Unit Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Perttu
authors.initials: P
authors.lastname: Koskenvesa
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Internal Medicine V, Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Gunther
authors.initials: G
authors.lastname: Gastl
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, "Seràgnoli" Institute of Hematology, "S. Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Novartis Oncology Italy, Origgio, VA, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Haenig
authors.affiliation: Klinik für Innere Medizin II/Hämatologie, Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib
keywords: Chronic myeloid leukemia; Clinical trial; Frontline; Impact of age; Molecular response; Nilotinib