title: Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach.
abstract: BACKGROUND
  The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important.
  
  
  METHODS
  s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine-based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria.
  
  
  RESULTS
  Complete remission rates were statistically lower in the HMA group (36%) versus the IC (46%), CPX-351 (45%), and LDAC groups (43%). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P = .048). Only 4.3% of the IC patients proceeded to transplantation, whereas 10.3% of the patients on lower intensity regimens did (P = .001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P = .75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis.
  
  
  CONCLUSIONS
  Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies. Cancer 2017;123:3050-60. © 2017 American Cancer Society.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Prajwal Chaitanya
authors.initials: PC
authors.lastname: Boddu
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: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kapil
authors.initials: K
authors.lastname: Bhalla
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Courtney D
authors.initials: CD
authors.lastname: DiNardo
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Maro
authors.initials: M
authors.lastname: Ohanian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
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
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Tapan M
authors.identifier: http://orcid.org/0000-0002-9892-9832
authors.initials: TM
authors.lastname: Kadia
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage*; D000077209:Decitabine; D005260:Female; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000235:genetics; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D000077209:Decitabine; D001374:Azacitidine
keywords: CPX-351; acute myelogenous leukemia; epigenetic; hypomethylating; intensive; low-dose cytarabine; outcomes; secondary