title: Exploratory study on the impact of switching to nilotinib in 18 patients with chronic myeloid leukemia in chronic phase with suboptimal response to imatinib.
abstract: BACKGROUND
  The phase II, exploratory, open-label Exploring NilotinibBCR-ABLEffects (ENABL) study [ClinicalTrials.gov identifier: NCT00644878] assessed the impact of switching to nilotinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) who had a suboptimal molecular response with imatinib.
  
  
  METHODS
  Patients with CML-CP who had previously achieved a complete cytogenetic response (CCyR), but had a suboptimal molecular response, with frontline imatinib therapy (N= 18) were assigned to receive nilotinib 300 mg twice daily. The primary endpoint was the change inBCR-ABL1transcript levels from baseline after 12 months; rates of major molecular response (MMR) and safety were also assessed.
  
  
  RESULTS
  At 3 months after switching to nilotinib, 10 of 17 (59%) evaluable patients had achieved MMR. At 12 months, 9 of 12 (75%) evaluable patients had achieved MMR, and the medianBCR-ABL1level among all patients remaining in the study was 0.020% on the International Scale (IS), equivalent to a 3.7-log reduction from the standardized IS baseline (primary endpoint). Adverse events (AEs) were typically grade 1/2 and manageable with dose interruptions. A total of three patients experienced serious study drug-related AEs, including pancreatitis, bradycardia, and vertigo. No deaths were reported.
  
  
  CONCLUSIONS
  Overall, results from this exploratory study suggest that switching to nilotinib due to suboptimal molecular response with imatinib can result in improved molecular response for patients with CML-CP.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Sikander
authors.initials: S
authors.lastname: Ailawadhi
authors.affiliation: Department of Hematology, Indiana Blood and Marrow Transplantation, Indianapolis, IN, USA.
authors.forename: Luke P
authors.initials: LP
authors.lastname: Akard
authors.affiliation: Departments of Internal Medicine and Medical Oncology, St. Agnes Hospital, Baltimore, MD, USA.
authors.forename: Carole B
authors.initials: CB
authors.lastname: Miller
authors.affiliation: Department of Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Jillella
authors.affiliation: Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Solveig G
authors.initials: SG
authors.lastname: Ericson
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Felice
authors.initials: F
authors.lastname: Lin
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Warsi
authors.affiliation: Clinical Cancer Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Jerald
authors.initials: J
authors.lastname: Radich
keywords: CML-CP; ENABL; imatinib; nilotinib; suboptimal response; switch; tyrosine kinase inhibitor