Substitution of Clofarabine for Anthracycline/Etoposide in Induction Therapy for Pediatric Acute Myeloid Leukemia


Key Points

  • Clo+AraC was associated with a higher day 22 MRD-positive rate vs HD-ADE.
  • No significant differences were observed in MRD-positive rates after induction II, complete remission after induction II, event-free survival, or overall survival.

In the phase III AML08 trial reported in the Journal of Clinical Oncology, Rubnitz et al found that the use of clofarabine instead of an anthracycline and etoposide in the first course of induction therapy may be a feasible strategy in pediatric patients with acute myeloid leukemia.

The trial, which took place between 2008 and 2017, included 262 patients with previously untreated disease aged < 22 years from eight sites (seven in the United States, one in Singapore). Patients were randomly assigned to receive clofarabine and cytarabine (Clo+AraC, n = 129) or high-dose cytarabine, daunorubicin, and etoposide (HD-ADE, n = 133) as induction course I. Induction II consisted of low-dose ADE alone or in combination with sorafenib or vorinostat. Consolidation consisted of two or three additional courses of chemotherapy or hematopoietic cell transplantation.

The primary endpoint was minimal residual disease (MRD) at day 22.

MRD and Other Treatment Outcomes

Day 22 MRD was positive in 57 (47%) of 121 evaluable patients in the Clo+AraC group vs 42 (35%) of 121 evaluable patients in the HD-ADE group (odds ratio [OR] = 1.86, P = .04). After completion of induction II, MRD positivity was found in 24 (20%) of 119 patients vs 16 (14%) of 115 patients (OR = 1.62, P = .26). The complete remission rate after two courses of induction therapy was 93.0% vs 92.5% (P = 1.0). 

With median follow-ups of 1,378 and 1,064 days for survivors in the Clo+AraC group and HD-ADE group, 3-year event-free survival was 52.9% vs 52.4% (P = .94), 3-year cumulative incidence of relapse was 25.3% vs 28.6% (P = .54), and 3-year overall survival was 74.8% vs 64.6% (P = .1).

The investigators concluded, “Our findings suggest that the use of clofarabine with cytarabine during remission induction might reduce the need for anthracycline and etoposide in pediatric patients with acute myeloid leukemia and may reduce rates of cardiomyopathy and treatment-related cancer.”

Jeffrey E. Rubnitz, MD, PhD, of the Department of Oncology, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by a grant from the National Institutes of Health and by the American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit

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