title: Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation.
abstract: BACKGROUND
  Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT).
  
  
  METHODS
  A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported.
  
  
  RESULTS
  After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]).
  
  
  CONCLUSIONS
  Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875-80. © 2017 American Cancer Society.
authors.affiliation: Hematology Department, Lyon South-Pierre-Bénite Hospital Center and Unit 1052, National Institute of Health and Medical Research Lyon Cancer Research Center/Léon Berard Center, Lyon, France.
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.affiliation: Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Grzegorz W
authors.initials: GW
authors.lastname: Basak
authors.affiliation: Leukemia Research Institute, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Haematology, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Javier
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.affiliation: Department of Haematology, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.affiliation: Department of Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Department of Haematology and Medical Oncology, University of Leipzig, Leipzig, Germany.
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Department of Leukemia, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mauro
authors.affiliation: Department of Haematology, Singapore General Hospital, Duke-NUS Medical School, Singapore.
authors.forename: Charles
authors.initials: C
authors.lastname: Chuah
authors.affiliation: Clinic and Polyclinic for Internal Medicine II, Division of Hematology and Oncology, Jena University Hospital, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: L. e A. Seragnoli Institute of Hematology, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Analysis Group, Inc, Boston, Massachusetts.
authors.forename: Maral
authors.initials: M
authors.lastname: DerSarkissian
authors.affiliation: Analysis Group, Inc, Boston, Massachusetts.
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
authors.affiliation: ARIAD Pharmaceuticals, Inc, Cambridge, Massachusetts.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McGarry
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001752:Blast Crisis / Q000235:genetics / Q000628:therapy*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000628:therapy*; D016016:Proportional Hazards Models; D011724:Pyridazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011724:Pyridazines; C545373:ponatinib
keywords: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); allogeneic stem cell transplantation (allo-SCT); chronic myeloid leukemia (CML); ponatinib; threonine to isoleucine mutation at codon 315 (T315I)