title: Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib.
abstract: Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials-Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1(IS) ≤0.0032%; MR(4.5)) and those without major molecular response at study start, MR(4.5) by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877.
authors.affiliation: South Australian Health and Medical Research Institute, Division of Haematology and Centre for Cancer Biology, South Australia Pathology, University of Adelaide, Adelaide, Australia;
authors.forename: Timothy P
authors.identifier: http://orcid.org/0000-0002-7990-4509
authors.initials: TP
authors.lastname: Hughes
authors.affiliation: Princess Margaret Hospital, Leukemia Clinic, Blood and Marrow Transplant Centre, Apheresis Unit, Toronto, ON, Canada;
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Universidade Federal do Rio de Janeiro, Department of Clinical Medicine, Rio de Janeiro, Brazil;
authors.forename: Nelson
authors.initials: N
authors.lastname: Spector
authors.affiliation: Hospital Clínic L'Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain;
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: Universidade Federal do Paraná, Hospital de Clinicas, Curitiba, Paraná, Brazil;
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
authors.affiliation: Hospital Das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;
authors.forename: Nelma Cristina D
authors.initials: NC
authors.lastname: Clementino
authors.affiliation: Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo, Hematology Department, São Paulo, Brazil;
authors.forename: Pedro Enrique
authors.initials: PE
authors.lastname: Dorlhiac Llacer
authors.affiliation: Hematology Department, Alfred Hospital, Melbourne, Australia;
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Schwarer
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Bordeaux and Laboratoire Hématopoïèse Leucémique et Cible Thérapeutique, Biothérapies des Maladies Génétiques et Cancers, Inserm U1035, Université Bordeaux Ségalen, Bordeaux, France;
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.affiliation: Service des Maladies du Sang et EA3518, Hôpital Saint-Louis, Paris, France;
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: Centre for Cancer Biology, South Australia Pathology, University of Adelaide, Adelaide, Australia;
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ; and.
authors.forename: Das
authors.initials: D
authors.lastname: Purkayastha
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ; and.
authors.forename: LaTonya
authors.initials: L
authors.lastname: Collins
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ; and.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczudlo
authors.affiliation: McMaster University and Juravinski Hospital and Cancer Centre, Hamilton, ON, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Leber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D057915:Drug Substitution; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
chemical_list: C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib