Background: The “3+7” chemotherapy regimen is the standard for newly diagnosed acute myeloid leukemia (ND-AML). New therapeutic agents have made exploring alternative intensive chemotherapy (IC) regimens viable. The VIALE-A study explored chemo-free treatments; however, real-world outcomes with Venetoclax and Azacitidine (VA) were suboptimal, with response rates of 44% and 66.4%. The VA regimen also shows resistance in specific AML subtypes. Combining VA with the histone deacetylase inhibitor (HDACi) Chidamide may address these limitations. This study retrospectively analyzes the efficacy and safety of the ABC-14 regimen in a real-world setting.

Aim: To evaluate the treatment response and adverse effects of the ABC-14 regimen in newly diagnosed AML patients under real-world conditions and compare outcomes with the historical IC regimen.

Methods: From April 1, 2023, to May 30, 2024, 110 newly diagnosed AML patients received the ABC-14 regimen across 16 centers in the ABC-14 collaboration group, with 104 completing response assessments. Additionally, 206 newly diagnosed AML patients who underwent IC treatment, sourced from the Southern Leukemia Collaborative Group database (2010-2013) and the GDPH AML database, served as the control group.

Treatment Protocol: The ABC-14 regimen included Azacitidine 75 mg/m² (days 1-7), Venetoclax 100 mg (day 1), 200 mg (day 2), and 400 mg (days 3-14), and Chidamide 5 mg (days 1-6 weekly for two weeks, then a two-week rest). The traditional “3+7” IC regimen included Idarubicin 10 mg/m² (days 1-3), Mitoxantrone 10 mg/m² (days 1-3), and Cytarabine 100 mg/m² (days 1-7).

Results: Baseline characteristics differed between groups: the ABC-14 group had older patients, a higher prevalence of the M4/M5 subtype, and adverse ELN risk, while the IC group had more AML1-ETO subtype cases. The CRc (complete remission, complete remission with incomplete blood count recovery, and morphologic leukemia-free state) rate did not differ significantly after cycle-1 (67.6% vs. 73.0%, P = 0.330) or cycle-2 (75.2% vs. 78.1%, P = 0.579). Among CRc patients, the MRD-negative rate was 70% in the ABC-14 group, compared to 77.1% in the IC group (P = 0.285). The ABC-14 regimen showed superior efficacy in patients with IDH1/2 mutations (95.2%), and three out of four patients with TP53 abnormalities achieved CRc.

The ABC-14 regimen showed enhanced efficacy in elderly (≥60 years) and unfit AML patients, with CRc rates of 64% and 72.5%, respectively. In patients under 60 years and fit for IC therapy, the ABC-14 regimen displayed comparable efficacy to IC, with CRc rates of 72% and 68.6%, respectively. With continued treatment cycles, cumulative CRc rates increased to 82.9% and 87% in the ABC-14 regimen group, with no significant difference compared to the IC group (75.7%, P = 0.356). Factors such as age (P = 0.565), ELN stratification (P = 0.810), and fit/unfit status (P = 0.111) did not significantly affect CRc outcomes.

As of July 25, 2024, the median duration of remission and overall survival (OS) had not been reached in the ABC-14 cohort. Grade 3 or 4 hematologic adverse events occurred in 81.2% of patients. The median recovery times for neutrophils and platelets were 23 days (range: 0-52) and nine days (range: 0-52), respectively. Neutropenia lasted significantly longer in the ABC-14 group than in the IC group (19.41 vs. 11.78 days, P < 0.001), while platelet recovery time was similar (11.96 vs. 14.28 days, P = 0.616). The most common non-hematologic toxicity was grade 3-4 infection (73.6%), followed by elevated liver enzymes and serum creatinine (10% each), all resolving spontaneously. The median follow-up duration for the ABC-14 group was 134 days (range: 24-470). Six patients had died by the last follow-up; five deaths occurred between 30 and 60 days, with causes including infection, cerebral hemorrhage, and disease progression. No early deaths occurred within the first four weeks.

Conclusions: This real-world retrospective study indicates that the ABC-14 regimen's induction efficacy is comparable to the traditional “3+7” regimen, particularly in M4/M5 subtypes and FLT3-mutated AML. The regimen also showed promise in patients with TP53 abnormalities. However, for AML1-ETO and MLL rearrangement subtypes, the traditional IC induction regimen remains reliable. Further randomized controlled trials (NCT06451861) are needed to define the efficacy and safety profile of the ABC-14 regimen.

Disclosures

No relevant conflicts of interest to declare.

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2024
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