Daunorubicin and Cytarabine 3+5 Combined with Venetoclax in De Novo Patients with Acute Myeloid Leukemia: A Single-Center, Open-Label, Controlled Study

Background: Daunorubicin and cytarabine 3+5 were the standard first-line induction chemotherapy in newly diagnosed acute myeloid leukemia currently, whereas the complete remission rate is only 70%. In order to detect a more effective and tolerated induction regime, we designed a novelty regime of daunorubicin and cytarabine 3+5 combined with venetoclax as the induction chemotherapy in de novo patients with acute myeloid leukemia, and to evaluate the efficacy and safety of this regime.

Methods: We conducted a single-institutional, non-randomized, open-label, controlled study. We enrolled patients with de novo AML aged between 18 and 60 years and ECOG score was 0-2. The test group received daunorubicin 40mg/m²/d, d1~d3; cytarabine 100mg/m²/d, d1~d5, venetoclax 100mg d1, 200mg d2, 400mg d3 ~d14, whereas the control group received daunorubicin 60mg/m²/d, d1~d3 and cytarabine 100mg/m²/d, d1~d7. The induction chemotherapy length of the two groups was 28 days per cycle, and all patients received one or two cycles of induction chemotherapy. Subsequently, these patients received sustained chemotherapy or hematopoietic stem cell transplantation. The primary endpoint was the complete remission rate after two cycles of induction therapy, the secondary endpoints were adverse events and overall survival.

Results: Between December 2021 and June 2024, forty patients with newly diagnosed acute myeloid leukemia at the first affiliated hospital of Anhui Medical University were enrolled. Twenty-one patients were in the test group and nineteen in the control group. There were 25 males and 15 females, with a median age of 46 (range 18-59) years old in both groups. The baseline characteristics were all balanced differently between the two groups. After two cycles of induction chemotherapy, the complete remission rate was 95% (20 of 21 patients) in the test group, whereas the complete remission rate was 68% (13 of 19 patients) in the control group (P＝0.0395). The most common hematological adverse events were neutropenia, thrombocytopenia, and anemia. The most frequent non-hematological adverse events include infections, vomiting, diarrhea, and hypokalemia. Infection rate was 95% in the test group and 100% in the control group. Fatal adverse events did not occur in both groups. At the median follow-up of 14 months, the median overall survival was not reached in both groups. The estimated 2-year overall survival rate was 72% in the test group and 58% in the control group, respectively.

Conclusions: Daunorubicin and cytarabine 3+5 combined with venetoclax is an effective induction therapy for de novo patients with acute myeloid leukemia, and is well tolerated for these patients in the induction chemotherapy periods.

No relevant conflicts of interest to declare.