title: Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study.
abstract: The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.
authors.affiliation: Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Department of Hematology and Oncology, University of Bologna, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: N C P
authors.initials: NC
authors.lastname: Cross
authors.affiliation: Hospital Universitario de la Princesa, IIS-IP, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Steegmann
authors.affiliation: Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Ossenkoppele
authors.affiliation: Ion Chiricuta Institute of Oncology, Cluj, Romania.
authors.forename: L
authors.initials: L
authors.lastname: Petrov
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: Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Vilnius University Hospital Santariskiu Klinikos, Vilnius University, Vilnius, Lithuania.
authors.forename: L
authors.initials: L
authors.lastname: Griskevicius
authors.affiliation: Department of Hematology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Wiktor-Jedrzejczak
authors.affiliation: Service d'Hématologie Adulte et INSERM UMR1160, Hôpital Saint-Louis, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Rea
authors.affiliation: Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: D
authors.initials: D
authors.lastname: Coriu
authors.affiliation: Universitätsklinikum RWTH Aachen, Aachen, Germany.
authors.forename: T H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Porkka
authors.affiliation: Division of Internal Medicine & Hematology, University of Turin, Orbassano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Gastl
authors.affiliation: Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Müller
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Schuld
authors.affiliation: Novartis Oncology Region Europe, Origgio, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Di Matteo
authors.affiliation: Novartis Oncology Region Europe, Origgio, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pellegrino
authors.affiliation: Novartis Oncology Region Europe, Origgio, Italy.
authors.forename: L
authors.identifier: http://orcid.org/0000-0003-2047-2526
authors.initials: L
authors.lastname: Dezzani
authors.affiliation: Laboratoire Hématopoïèse Leucémique et Cible Thérapeutique, Université Victor Ségalen, Bordeaux, France.
authors.forename: F-X
authors.initials: FX
authors.lastname: Mahon
authors.affiliation: Department of Hematology and Oncology, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Baccarani
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib