DAC+CAG Compared with the Standard 3+7 Regimen for Induction of the Medically Fit Elderly Acute Myeloid Leukemia: An Open-Label, Multicenter, Randomized, Phase III Trial

Background: Elderly subjects with acute myeloid leukemia have a very poor prognosis,only 40%-60% achieving a complete remission(CR) with intensive chemotherapy. Hypomethylating agents such as decitabine show activities in elderly AML cases. Method:This multicenter, open-label, randomized phase III trial compared the outcomes between decitabine combined with modified CAG regimen (DAC+CAG) and standard daunorubicin or idarubicin plus cytarabine (3+7) for medically fit elderly AML patients.Patients were randomly assigned to the two group in 1:1 ratio approximately. Results: A total of 110 newly diagnosed AML patients selected according to age (range 60-75), performance status (PS≤2), Charlson Comorbidity Index (CCI≤2) were analyzed.CR rate was 58.2% and 61.8% after the first cycle(P=0.963), and 70.9% and 69.1% after two cycles(p=0.780), respectively,in the DAC+CAG group and 3+7 group. There was no statistically difference of ORR after two cycles between the two groups (74.5% vs 76.4%,P=1.000).With a median follow-up of 18 months, the 1-year,3-year OS was 67.4% (95% CI:53.7-81.1%),38.9% (95% CI:16.8-61%) and 55.7%(95% CI:42-69.4%),37.6% (95% CI:20-54.8%) in the DAC+CAG and 3+7 group,respectively(p=0.383).And the 1-year,3-year LFS was 66.8% (95% CI:51.9-81.7%),34.2% (95% CI:22.2-64.2%) and 55.7% (95% CI:40-69.4%),35.8% (95% CI: 19.2-52.4%) in the two groups,respectively(p=0.255). Grade 3 or worse adverse events ,such as neutropenia (38 [69.1%] vs 46 [83.6%]), thrombocytopenia (38 [69.1%] vs 46 [83.6%]),infections(17 [30.9%] vs 25 [45.5%]) and septicemia(3[5.5%] vs 11 [20%]) are more common in 3+7 group than DAC+CAG group.The 8-week cumulative incidence of induction chemotherapy-related mortality(iTRM) were 5.5% and 12.7% (p=0.069) in DAC+CAG and 3+7 groups, respectively.Multivariate analysis revealed that allo-HSCT(p=0.004,HR=0.327,95%CI:0.152-0.703) and after first cycle achieved CR(CR1)(p=0.005,HR=0.348,95%CI:0.166-0.732) were favourable factors for OS,and the latter was also identified as a favourable factor for LFS (p=0.013,HR=0.480,95%CI:0.173-1.331). Conclusion: DAC+CAG regimen showed a similar CR rate and encouraging survival compared with the 3+7 regimen,it seems be a safe and effective regimen for medically fit older patients with AML.

Keywords:Acute myeloid leukemia, Elderly, DAC+CAG regimen, 3+7 regimen,medically fit patients