Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status

  • Gail J. Roboz
    Weill Cornell Medicine, New York, NY;
  • Farhad Ravandi
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
  • Andrew H. Wei
    Department of Clinical Haematology, The Alfred Hospital, Melbourne, Australia;
  • Hervé Dombret
    Hematology, Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France;
  • Felicitas Thol
    Medizinische Hochschule Hannover, Hannover, Germany;
  • Maria Teresa Voso
    Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy;
  • Andre C. Schuh
    Princess Margaret Cancer Centre, Toronto, Canada;
  • Kimmo Porkka
    Hospital District of Helsinki and Uusimaa (HUS) Comprehensive Cancer Center, Hematology Research Unit Helsinki and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki, Finland;
  • Ignazia La Torre
    Celgene, a Bristol Myers Squibb Company, Boudry, Switzerland;
  • Barry Skikne
    Division of Hematologic Malignancies and Cellular Therapeutics, BMS, Princeton, NJ;
  • Jianhua Zhong
    Division of Hematologic Malignancies and Cellular Therapeutics, BMS, Princeton, NJ;
  • C. L. Beach
    Division of Hematologic Malignancies and Cellular Therapeutics, BMS, Princeton, NJ;
  • Alberto Risueño
    BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol Myers Squibb Company), Seville, Spain;
  • Daniel L. Menezes
    Division of Hematologic Malignancies and Cellular Therapeutics, BMS, Princeton, NJ;
  • Gert Ossenkoppele
    Amsterdam UMC, Location VUMC (Vrije Universiteit Medical Center), Amsterdam, The Netherlands; and
  • Hartmut Döhner
    Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany

抄録

<jats:title>Abstract</jats:title><jats:p>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 &gt;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.</jats:p>

収録刊行物

  • Blood

    Blood 139 (14), 2145-2155, 2022-04-07

    American Society of Hematology

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