title: Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis.
abstract: OBJECTIVE
  The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia.
  
  
  METHODS
  Patients received nilotinib 300 mg twice daily, up to 24 months.
  
  
  RESULTS
  At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Ph-/BCR-ABL1 + subgroup, 30 patients had safety assessments and 28 were followed up for molecular assessments. At 18 months, the molecular response (MR) 4 rate [MR4; BCR-ABL1 ≤0.01% on International Scale (IS)] was similar in the Ph-/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1IS≤0.1%;), MR4, and MR4.5(BCR-ABL1IS≤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Ph-/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Ph-/BCR-ABL1 + and Ph+ subgroups, rash (20 and 22%), pruritus (16.7 and 16.7%), nasopharyngitis (13.3 and 10.4%), fatigue (10 and 14.2%), headache (10 and 15.8%), and nausea (6.7 vs 11.4%) were frequent non-hematologic adverse events, whereas hypophosphatemia (23.3 and 6.8%), anemia (10 and 6.5%), and thrombocytopenia (3.3 and 10.2%) were the common hematologic/biochemical laboratory events.
  
  
  CONCLUSIONS
  Based on similar molecular response and safety results in both subgroups, we conclude that Ph-/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.
authors.affiliation: Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany. andreas.hochhaus@med.uni-jena.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Laboratoire Hématopoïèse Leucémique et Cible Thérapeutique, Université Victor Ségalen, Bordeaux, France.
authors.forename: Franҫois-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.affiliation: Charité-Universitätsmedizin Berlin Campus Virchow, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: Ion Chiricuta Institute 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: Jeroen J W M
authors.initials: JJWM
authors.lastname: Janssen
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nicholas C P
authors.initials: NCP
authors.lastname: Cross
authors.affiliation: Adult Hematology Department, Hôpital Saint-Louis, APHP, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", "S Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Department of Hematology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", "S Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Department of Hematology, Oncology, and Clinical Immunology, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gattermann
authors.affiliation: Servicio de Hematología y Hemoterapia, IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Maria Liz Paciello
authors.initials: MLP
authors.lastname: Coronel
authors.affiliation: Hospital de Donostia, San Sebastian, Spain.
authors.forename: Maria Asuncion Echeveste
authors.initials: MAE
authors.lastname: Gutierrez
authors.affiliation: Servicio de Hematología y Hemoterapia, IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Valentin
authors.initials: V
authors.lastname: Garcia-Gutierrez
authors.affiliation: Novartis Oncology Region Europe, Origgio, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Novartis Oncology Region Europe, Origgio, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Dezzani
authors.affiliation: Division of Hematology Oncology, Developmental Therapeutics Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D010677:Philadelphia Chromosome; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib
keywords: Chronic myeloid leukemia; ENEST1st; Nilotinib; Philadelphia chromosome negative/BCR-ABL positive