Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status. Academic Article uri icon

Overview

abstract

  • Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD- status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD- during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity >6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. Registered at clinicaltrials.gov as #NCT01757535.

authors

  • Roboz, Gail J
  • Ravandi, Farhad
  • Wei, Andrew H
  • Dombret, Hervé
  • Thol, Felicitas
  • Voso, Maria Teresa
  • Schuh, Andre C
  • Porkka, Kimmo
  • La Torre, Ignazia
  • Skikne, Barry
  • Zhong, Jianhua
  • Beach, C L
  • Risueño, Alberto
  • Menezes, Daniel L
  • Ossenkoppele, Gert
  • Döhner, Hartmut

publication date

  • April 7, 2022

Research

keywords

  • Hematopoietic Stem Cell Transplantation
  • Leukemia, Myeloid, Acute

Identity

Scopus Document Identifier

  • 85127514287

Digital Object Identifier (DOI)

  • 10.1182/blood.2021013404

PubMed ID

  • 34995344

Additional Document Info

volume

  • 139

issue

  • 14