(ChemotherapyAdvisor) – Younger age, favorable-risk acute myeloid leukemia (AML), and treatment with idarubicin compared with high-dose daunorubicin predict a better long-term outcome in patients aged 50 years and older, investigators reported in the Journal of Clinical Oncology online December 17.
“Although standard chemotherapy remains associated with a poor outcome in older patients with AML, it is unclear which patients can survive long enough to be considered as cured,” noted Claude Gardin, MD, Department of Hematology, Hôpital Avicenne, Bobigny, France, and colleagues. “Older patients with AML typically have malignant disease, for which the high rate of short-term treatment failure may hinder the identification of factors influencing long-term survival.”
To identify factors associated with prolonged long-term survival and possibility of cure, the investigators conducted a prognostic analysis of 727 older patients with AML (median age, 67 years) treated in two idarubicin versus daunorubicin Acute Leukemia French Association trials.
“Cure fraction analysis allowed us to better identify, among known covariates, those only influencing median OS of patients who will die, as opposed to covariates influencing the long-term and potential cure,” Dr. Gardin noted.
Complete remission (CR) rate and overall survival (OS) were influenced by age, WBC count, secondary AML, ECOG performance status, and adverse-risk and favorable-risk AML subsets (European LeukemiaNet classification), they found. Patients randomly assigned to receive idarubicin had a higher CR rate, but not longer OS (P=0.13); overall cure rate was 13.3% (95% CI 10.4-16.2).
Older age (P<0.001) and ECOG-PS >1 (P<0.001) had a negative influence on the cure rate, “which was higher in patients with favorable-risk AML (39.1% vs 8.0% in adverse-risk AML; P<0.001) and those treated with idarubicin (16.6% vs 9.8% with DNR; P=0.018),” they wrote.
Long-term impact of idarubicin was observed in patients <65 years; all patients in the control arm received high doses of daunorubicin (cure rate, 27.4% for idarubicin vs 15.9% for daunorubicin; P=0.049).
“In multivariate analysis, idarubicin random assignment remained associated with a higher cure rate (P=0.04), together with younger age and favorable-risk AML, despite not influencing OS (P=0.11),” they reported.
“As illustrated by this comparison of the old drugs, such as daunorubicin and idarubicin, cure rate improvement might become a relevant clinical end point,” Dr. Gardin concluded. “This may add significant information when gains in median survival, which are often modest, are evidenced by standard survival analysis. This may also be considered when evaluating costly new drugs in AML, such as hypomethylating agents and clofarabine.”