Efficacy of Decitabine in Combination with IA Versus IA in Patients with Newly Diagnosed AML, a Multicenter, Prospective, Randomized Controlled Trial

Introduction:

Decitabine is currently primarily used to treat elderly acute myeloid leukemia (AML) patients and above or those who are intolerant to standard chemotherapy. To optimize the induction regimen for younger AML patients and explore the optimal use of decitabine, this study conducted a multicenter, prospective, randomized controlled clinical trial evaluating the combination of decitabine with the IA (DIA) regimen in newly diagnosed younger AML patients, furthermore, investigating the predictive value of BTG1 levels before and after treatment with decitabine combined with the IA regimen.

Methods:

This is a multicenter randomized controlled clinical trial conducted across 4 hospitals from May 2019 to April 2024 (ChiCTR2000037928). This study employed a randomized controlled design to allocate newly diagnosed AML patients into experimental and control groups. Patients in the experimental group received DIA regimen, specifically decitabine at 20 mg/m²/day on days 1 to 5 along with IA regimen (cytarabine 100-200 mg/m²/day on days 4 to 10 and idarubicin 10 mg/m²/day on days 4 to 6). Patients in the control group received the IA regimen alone.

Subsequently, a single-arm study employing a DIA regimen was conducted to investigate whether pre- and post-treatment levels of BTG1 can predict efficacy. The Kendall's rank correlation coefficient was used to analyze the correlation between BTG1 levels and efficacy outcomes.

Results:

This study included 106 evaluable newly diagnosed AML patients, with a gender ratio of 1:1.06 and a median age of 44 years. 55 patients were randomly assigned to the experimental group, and 51 to the control group. There were no significant differences between the two groups of patients in baseline characteristics except that the control group had significantly higher platelet counts at initial diagnosis compared to the experimental group (61.0 vs. 34.0, P =0.005).

After one cycle of treatment, 44 patients (80.0%) in the experimental group achieved complete remission (CR) /CR with incomplete hematologic recovery (CRi), and 9 patients (16.4%) achieved partial remission (PR), resulting in an overall response rate (ORR) of 96.4%. In the control group, 43 patients (84.3%) achieved CR/CRi, and 4 patients (7.8%) achieved PR, resulting in an ORR of 92.1%. Among patients achieving CR, 30 (68.2%) patients in the experimental group achieved deep remission (CR_MRD-), which was higher than the 22 patients (51.2%) in the control group, though this difference did not reach statistical significance.

There were no significant differences between the two groups of patients in terms of hematologic and non-hematologic adverse events (AEs). At the end of follow-up, in the experimental group and the control group, 31 (56.4%) and 38 (74.5%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) (P＞0.05). In the experimental group, 42 patients (76.4%) were alive, compared to 42 patients (82.4%) in the control group. The two-year overall survival (OS) was 78.4% in the experimental group and 84.3% in the control group (P＞0.05). The two-year relapse-free survival (RFS) rates were 75.5% in the experimental and 74.2% in the control groups(P＞0.05).

Thirty-seven patients treated with DIA regimen were enrolled in a single-arm study to investigate whether BTG1 levels before and after treatment could predict efficacy. Pre-treatment levels of BTG1 are negatively correlated with achieving MRD negativity post-treatment (r=-0.285, P=0.039).

Conclusion:

In newly diagnosed non-elderly AML patients, receiving DIA regimen as an induction therapy did not significantly increase adverse reactions compared to the IA regimen alone, demonstrating good tolerability. The DIA regimen did not show clear advantages in terms of CR, OS, and RFS. However, DIA regimen shows a higher rate of achieving MRD-negative CR, providing a foundation for long-term survival in patients, yet the difference lacks statistical significance, indicating the need for further expansion of the sample size. Therefore, its clinical application in newly diagnosed non-elderly patients still requires sufficient clinical research evidence and personalized selection. Pre-treatment BTG1 levels predict the potential for achieving MRD negativity in patients treated with DIA regimen.