Determining Optimal Daunorubicin Dosing and 7 + 3 Induction Cycles for Frontline AML Treatment

According to results from a randomized controlled trial, the use of high-dose (90 mg/m²) daunorubicin once daily in the context of a classical 7 + 3 induction cycle did not significantly improve early response rates among patients with newly diagnosed acute myeloid leukemia (AML) and did not lead to higher remission rates or longer survival than the standard dosing of 60 mg/m² once daily.

Additionally, among those patients with solid response after their first induction, a following induction yielded limited impact on relapse-free survival (RFS) and demonstrated no overall survival (OS) benefit.

“To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m² with 90 mg/m² daunorubicin in the first 7 + 3 induction and 1 versus 2 cycles of 7 + 3 induction,” stated lead study author Christoph Röllig, MD, MSc, University Hospital TU Dresden, Dresden, Germany, and coauthors.

Investigators included 864 patients aged 18 to 65 years with newly diagnosed AML who were randomly assigned to 60 vs 90 mg/m² daunorubicin once daily plus cytarabine. Additionally, patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle. Following a preplanned interim analysis demonstrating no significant difference in response between 60 and 90 mg/m², all consecutive patients received 60 mg/m² daunorubicin once daily.

Study results showed the proportion of good early responders was 44% versus 48% (P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P = .691); the 3-year RFS after 60 versus 90 mg/m² once daily was 54% versus 50% (P = .561), and the 3-year OS was 65% versus 58% (P = .242).

Furthermore, among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937).

“The use of 90 mg/m² daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m² once daily,” concluded Dr Röllig and colleagues.

Among patients with a good early response after the first induction, “a second induction has only a limited impact on RFS and does not result in an OS benefit,” they added.

Source:

Röllig C, Steffen B, Schliemann C, et al. Single or double induction With 7 + 3 containing standard or high-dose daunorubicin for newly diagnosed AML: the randomized DaunoDouble trial by the study alliance leukemia. JCO. Published online September 16, 2024. doi: 10.1200/JCO.24.00235