title: Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.
abstract: The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5(BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1IS⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).
authors.affiliation: Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Department of Haematology and Stem Cell Transplantation St István and St László Hospital, Budapest, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Masszi
authors.affiliation: Developmental Therapeutics Program, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Radich
authors.affiliation: SA Pathology, Adelaide, SA, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Ross
authors.affiliation: Hospital Universitario Doctor Negrin, Las Palmas de Gran Canaria, Spain.
authors.forename: M T
authors.initials: MT
authors.lastname: Gómez Casares
authors.affiliation: Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Stentoft
authors.affiliation: St James Hospital, Dublin, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Conneally
authors.affiliation: Servicio de Hematología, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: García-Gutiérrez
authors.affiliation: Universitätsklinikum Düsseldorf, Düsseldorf, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gattermann
authors.affiliation: Medical University of Warsaw, Department of Hematology, Warsaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Wiktor-Jedrzejczak
authors.affiliation: Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: P D
authors.initials: PD
authors.lastname: le Coutre
authors.affiliation: Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Martino
authors.affiliation: III. Med. Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Saussele
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: H D
authors.initials: HD
authors.lastname: Menssen
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.affiliation: Novartis Institute for Biomedical Research, Cambridge, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Krunic
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Bedoucha
authors.affiliation: University of Turin, Orbassano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Saglio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C498826:nilotinib