Venetoclax can bind to the BCL-2 protein, thereby initiating the apoptosis program and exerting anti-AML effects. The induction regimen combining venetoclax with hypomethylating agents (HMA) significantly improves the remission rate (over 60%) in elderly unfit AML patients and markedly prolongs survival in those achieving complete remission. Isocitrate dehydrogenase (IDH) 1 and 2 are involved in the citric acid cycle. Approximately 20% of AML patients carry IDH1 or IDH2 mutations, which lead to the reduction of α-ketoglutarate to 2-hydroxyglutarate (2-HG). 2-HG can cause histone methylation and inhibit TET2 activity, resulting in DNA hypermethylation, thereby affecting gene expression and cell differentiation. IDH mutations are more common in elderly patients and are often associated with cytogenetic abnormalities; they may also co-occur with FLT3-ITD, NPM1, or DNMT3A mutations. Ivosidenib is an IDH1 inhibitor, and previous studies have confirmed its safety and efficacy in AML treatment. According to adult AML treatment guidelines, IDH-mutated patients eligible for intensive chemotherapy may receive IDH inhibitors during induction therapy. Based on the study by Montesinos et al. on the role of ivosidenib and azacitidine in IDH-mutated AML, for patients ineligible for intensive chemotherapy, a new treatment option has been added: IDH1-mutated AML patients may receive ivosidenib (500 mg, days 1-28) combined with azacitidine (75 mg/m²/day for 7 days) in 28-day cycles, or ivosidenib monotherapy. Recent studies have shown that a triple-drug regimen comprising ivosidenib, venetoclax, and azacitidine demonstrates excellent efficacy and safety. In chemotherapy-ineligible patients, the triple regimen achieved a composite complete remission rate (CRc) of 86% and an overall response rate (ORR) of 92%. At a median follow-up of 27.4 months, the 2-year overall survival (OS) was 72%, and the 2-year event-free survival (EFS) was 72%. Therefore, this study aims to conduct a multicenter, single-arm clinical trial to preliminarily evaluate the long-term efficacy of this combination in adult AML.
Patients who meet AML according to WHO (2022) or AML and MDS/AML defined by ICC standards with IDH1 mutations detected by PCR or second-generation sequencing.
Age ≥14 years old, male or female.
The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.
Total bilirubin ≤ 1.5 times the upper limit of normal value (same age);
Acute promyelocytic leukemia with PML-RARA fusion gene
Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
Acute myeloid leukemia with BCR-ABL fusion gene
Treated patients (but can receive hydroxyurea or cytarabine to lower tumor burden).
Single group
Ivosidenib, Venetoclax, Azacitidine
DrugInduction therapy：Ivosidenib 500mg d1-28 Venetoclax 100mg d1，200mg d2，400mg d3, 800mg d4-14 Azacitidine 75mg/m2/d, d1-7 . Consolidation therapy: intermediate-dose cytarabine regimen ： 3 courses If IDH1 mutant residual disease was positive before consolidation chemotherapy, Ivosidenib was added; Maintenance treatment: Azacitidine、Venetoclax 、Ivosidenib： 6 courses
CRc rate
The ratio of patients achieved CR/CRh/CRi.
CRc MRD negtive rate by flow cytometry
The CRc MRD negtive rate was detected by flow cytometry after induction, consolidation and maintenance therapy.
CRc MRD negtive rate by PCR
The CRc MRD negtive rate was detected by PCR after induction, consolidation and maintenance therapy.
The maximum tolerated dose of ivosidenib and venetoclax combined with intensive chemotherapy
To determine the maximum tolerated dose of ivosidenib and venetoclax combined with intensive chemotherapy
Event-free survival (EFS)
The interval from the date of enrollment to the date of failed to achieve complete remission, the date of relapse, or the date of death, whichever occurred first.
overall survival
The interval from the date of enrollment to the date of death or the date of last follow-up, whichever occurred first.
Relapse free survival
The interval from CR to the date of relapse, or the date of death, or the date of last follow-up, whichever occurred first.
30-day mortality
Percentage of patients who died within 30 days from enrollment
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