Second cycle of 7+3 and outcomes in patients with newly diagnosed acute myeloid leukemia

Up to the present time, the association between timing of remission achievement and disease prognosis has not been evaluated in contemporary cohorts of patients with newly diagnosed acute myeloid leukemia (AML) treated with ‘7+3’ therapy. Megan Othus from Public Health Division and SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, and colleagues analyzed data from patients with AML enrolled in five SWOG trials between 1983–2015 to evaluate the relationship between outcomes and ‘7+3’ reinduction therapy. Data was published ahead of print in Leukemia.

The researchers studied 1,247 patients who received ‘7+3’ in five National Cancer Institute (NCI)/National Clinical Trials Network (NCTN) trials conducted by SWOG. The following studies were included in this analysis: S8600 (n = 530 patients, median age = 45 years [15–64]), S9031/S9333 (n = 156 patients, median age = 61 years [56–65]), S0106 (n = 301 patients, median age = 48 years [18–60]), and S1203 (n = 261 patients, median age = 48 years [19–60]).

The doses of chemotherapy regimens varied in these five trials. In S8600, S9031, and S9333, the cytarabine and daunorubicin doses were 200 mg/m² and 45 mg/m², respectively, whilst in S0106, administered doses were 100 mg/m² and 60 mg/m², respectively. Furthermore, in S1203, ‘7+3’ was administered as follows: cytarabine at a dose of 100 mg/m²  and daunorubicin at a dose of 90 mg/m².

Key findings:

• Complete remission (CR) achievement only upon reinduction chemotherapy was not significantly associated with either overall survival (OS): HR = 1.19 (95% CI, 0.89–1.59), P = 0.25; or relapse-free survival (RFS): HR = 1.15 (95% CI, 0.86–1.54), P = 0.34, in the older cohort of studies (S8600, S9031, and S9333)
• Administration of two cycles of induction chemotherapy before CR achievement was associated with inferior outcomes in the S0106 and S1203 trials
• CR achievement only upon reinduction chemotherapy showed significant correlation with inferior OS: HR = 1.82 (95% CI, 1.24–2.66), P = 0.002; or RFS: HR = 1.90 (95% CI, 1.34–2.70), P = 0.001

Those patients who achieved a morphologic CR with the first cycle of ‘7+3’ and also had available MRD data (n = 70) were further analyzed.

• Fifty-five patients with negative MRD tests after cycle 1 showed association with significantly better OS, P = 0.049; and better RFS, P = 0.098 compared to those 15 patients with positive MRD results after cycle 1
• Patients with MRD negativity after the first cycle of ‘7+3’ also had significantly superior RFS, P = 0.02; non-significant associations were found between MRD negativity and better OS, P = 0.11

This study indicates that early CR achievement after the first cycle of chemotherapy leads to better survival outcomes than two cycles of chemotherapy. These findings not only highlight “the prognostic significance of achieving a remission early but also support the value of MRD^neg CR as recently proposed by the European LeukemiaNet as new response entity.”