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Publications

Clinical Trial Journal Article Epublish

PubMed: 41890705 DOI: 10.1016/j.bneo.2026.100194

Survival after intensive therapy or clofarabine in fit older adults with acute myeloid leukemia: E2906 phase 3 trial.

Blood Neoplasia 3(2):100194

Authors: James M Foran, Zhuoxin Sun, Selina M Luger, David F Claxton, Hillard M Lazarus, Daniel A Arber, Jacob M Rowe, Elisabeth Paietta, Janis Racevskis, Fran Garrett-Bakelman, Yanming Zhang, Jessica K Altman, Aref Al-Kali, Hong Zheng, Keith W Pratz, E Randolph Broun, Bayard L Powell, Kristen Marie O'Dwyer, John E Godwin, Yishai Ofran, Mark R Litzow, Martin S Tallman

Affiliations

  • Division of Hematology and Medical Oncology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL.
  • ECOG-ACRIN Biostatistics Center, Dana-Farber Cancer Institute, Brookline, MA.
  • Division of Hematology-Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
  • Penn State Cancer Institute, Penn State Milton S. Hershey Medical Center, Hershey, PA.
  • Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH.
  • Department of Pathology, University of Chicago, Chicago, IL.
  • Shaare Zedek Medical Center, Jerusalem, Israel.
  • ECOG-ACRIN Leukemia Translational Laboratory, Montefiore Medical Center, Bronx, NY.
  • Division of Hematology and Medical Oncology, Department of Medicine, University of Virginia Cancer Center, Charlottesville, VA.
  • Memorial Sloan Kettering Cancer Center, New York, NY.
  • Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.
  • Division of Hematology, Mayo Clinic, Rochester, MN.
  • Sidney Kimmel Cancer Center. Johns Hopkins University, Baltimore, MD.
  • The Jewish Hospital, Cincinnati, OH.
  • Department of Cancer Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
  • Division of Hematology and Oncology, Department of Medicine, University of Rochester School of Medicine, Rochester, NY.
  • Providence Portland Medical Center, Portland, OR.

Abstract

Clofarabine is a second-generation purine nucleoside analog with encouraging reported 30-day induction mortality (IM) and complete remission (CR) or CRi (incomplete platelet recovery) rates, and represents a lower-intensity therapy for older adults with acute myeloid leukemia (AML). We evaluated long-term outcomes in a prospective phase 3 study using a noninferiority design. Patients aged ≥60 years with newly diagnosed AML and normal renal and cardiac function were randomized to standard intensive daunorubicin and cytarabine or single-agent clofarabine. The primary objective was overall survival (OS) using a weighted analysis. We incorporated prospective central testing for measurable residual disease (MRD; ≥0.1%) at remission using multiparameter flow cytometry. Among 727 patients (standard, n = 363; clofarabine, n = 364), there was no difference in CR/CRi (50%) or IM (8.5%) rates. The median follow-up was 58.6 months. In the primary analysis, OS was inferior with clofarabine (median, 10.4 vs 12.4 months [standard]; P = .04), although not in patients aged ≥70 years, with secondary AML, or unfavorable cytogenetics. Allogeneic transplantation was strongly associated with OS on multivariate analysis (HR, 0.53; P < .0001). MRD-negative remission was achieved in 41% of patients and strongly associated with 5-year OS irrespective of treatment (MRD-positive, 48.8% vs 12.2%; P = .003). In contrast, MRD-positive patients assigned to clofarabine (vs high-dose cytarabine) consolidation had significantly inferior OS. Clofarabine is inferior to standard intensive therapy despite similar remission rates. Achieving MRD-negative remission is associated with high, sustained rates of OS regardless of therapy. Increasing MRD negativity and improving outcomes among MRD-positive patients remain pressing, ongoing challenges. This trial was registered at www.clinicaltrials.gov as NCT02085408.

MeSH

Clofarabine, Cytarabine, Leukemia, Leukemia, Myeloid, Acute, Aged, Leukemia, Myeloid, Therapeutics