Combination Regimen Effective Induction Therapy for New Diagnosed AML

The regimen of daunorubicin, intravenous cytarabine, and oral venetoclax (DAV) may be an effective induction therapy for patients with newly diagnosed acute myeloid leukemia (AML), according to the results of a phase II trial.

“Daunorubicin (an anthracycline) and cytarabine, together referred to as the DA regimen (also known as the 3+7 regimen), has been the standard induction therapy in adult patients with AML for more than four decades,” study researchers wrote. However, novel regimens with higher complete remission rates and greater survival benefits are needed.

This study was a two-stage, single-arm, phase II trial conducted at three public hospitals in China. Enrolled patients were aged 18 to 60 years and had previously untreated AML. All patients received induction treatment with the DAV regimen: intravenous daunorubicin (60 mg/m² on days 1-3), intravenous cytarabine (100 mg/m² on days 1-7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6-11).

Among the 33 patients enrolled in the study, the composite complete remission rate after one cycle of DAV was 91%. The majority (97%) of patients who received complete remission had undetectable measurable residual disease.

Looking at response by risk, the composite complete remission rate was 100% in patients with favorable risk, 83% in those with intermediate risk, and 75% in those with adverse risk.

“A study completed by the U.S. Food and Drug Administration showed that patients who reach complete remission have improved overall survival compared with those who reach complete remission with incomplete blood cell count recovery or incomplete platelet recovery and patients who show no response,” the researchers wrote. “Therefore, a therapy in newly diagnosed AML that shows a benefit in complete remission rate could lead to an overall survival benefit.”

With a median follow-up of 11 months, the estimated one-year overall survival was 97%, and the one-year event-free survival was 72%.

All patients experienced grade 3 or worse neutropenia, thrombocytopenia, and anemia. There were no treatment-related deaths.

Based on these results, the researchers recommended a well-designed, randomized trial with long-term follow-up be conducted.

Wang H, Mao L, Yang M, et al. Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2022. doi: 10.1016/S2352-3026(22)00106-5