Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach

Cancer. 2017 Aug 15;123(16):3050-3060. doi: 10.1002/cncr.30704. Epub 2017 Apr 7.

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.

Keywords: CPX-351; acute myelogenous leukemia; epigenetic; hypomethylating; intensive; low-dose cytarabine; outcomes; secondary.

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Azacitidine / analogs & derivatives*
  • Azacitidine / therapeutic use*
  • Cytarabine / administration & dosage*
  • Decitabine
  • Female
  • Humans
  • Karyotype
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Second Primary / drug therapy*
  • Neoplasms, Second Primary / genetics
  • Proportional Hazards Models
  • Remission Induction
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Cytarabine
  • Decitabine
  • Azacitidine