(ChemotherapyAdvisor) – Adding the purine analog cladribine — but not fludarabine — to daunorubicin and cytarabine during induction has been found to increase complete remission rates and improve survival in adult patients with acute myeloid leukemia (AML), according to a study in the Journal of Clinical Oncology online April 16.

The investigators noted that these results suggest the daunorubicin/cytarabine/cladribine regimen be considered the new standard of care as remission induction.

The multicenter Phase 3 trial in Poland randomized 652 treatment-naïve patients with AML to one of three induction regimens: daunorubicin/cytarabine, daunorubicin/cytarabine/cladribine, or daunorubicin/cytarabine/fludarabine. Postremission treatment was the same for all arms. Median age of was 47 years (range, 17 to 60).

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Patients in the cladribine arm had a higher complete remission rate vs. daunorubicin/cytarabine alone (67.5% vs. 56%; P=0.01) as a consequence of reduced incidence of resistant disease (21% vs. 34%; P=0.004). No significant difference in early outcome between the daunorubicin/cytarabine and the fludarabine arms was observed.

Probability of overall survival was improved for the daunorubicin/cytarabine/cladribine arm (45% ± 4% at three years) vs. the daunorubicin/cytarabine arm (33% ± 4%; P=0.02); leukemia-free survival was comparable. Long-term outcome did not differ significantly when the daunorubicin/cytarabine and daunorubicin/cytarabine/fludarabine arms were compared.

Compared with the daunorubicin/cytarabine arm, a survival advantage of the addition of cladribine was observed among patients age 50 years or older (P=0.005), those with initial leukocyte count above 50×109/L (P=0.03), and those with unfavorable karyotype (P=0.03), the investigators found. In patients with adverse karyotype, the addition of fludarabine revealed a significant advantage over daunorubicin/cytarabine (P=0.02).

Hematologic and nonhematologic toxicities were comparable among treatment arms, indicating that the addition of purine analogs did not impair treatment tolerance.