Correlation between IDH1/2 Mutations and MRD Negativity in Unfit Acute Myeloid Leukemia Patients Treated with Venetoclax and Azacitidine: A Single-Center Case Series and Literature Review

Corresponding author: Huang Juan, huangjuanxy@med.uestc.edu.cn

DOI: 10.12201/bmr.202604.00020

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  Abstract: Objective:To investigate the predictive value of IDH1/2 mutations for measurable residual disease (MRD) negativity in unfit patients with acute myeloid leukemia (AML) receiving venetoclax (VEN) plus azacitidine (AZA), and to evaluate the impact of different VEN treatment durations (14-day vs. 28-day regimen).Methods:A retrospective analysis was conducted on 40 treatment-na?ve unfit AML patients who received VEN+AZA (14-day or 28-day regimen) at Sichuan Provincial Peoples Hospital.Clinical characteristics, treatment responses, and 180-day progression-free survival (PFS) were compared between the IDH1/2-mutated (n=13) and wild-type (n=27) groups. Multivariate logistic regression was performed to identify factors associated with MRD negativity. Stratified analysis by treatment regimen and a systematic literature review were conducted.Results:The incidence of IDH1/2 mutations was 32.5%. The CRc rate was 84.6% in the IDH1/2-mutated group and 77.8% in the wild-type group (P=1.000). Univariate analysis showed a higher MRD negativity rate in the mutated group (61.5% vs. 33.3%;OR=3.200，95%CI 0.810-12.650，P=0.171). After multivariate adjustment, IDH1/2 mutation maintained a positive trend toward MRD negativity (aOR=3.115, P=0.098). Stratified analysis revealed that among patients in the 28-day regimen group, those with IDH1/2 mutations had an MRD negativity rate of 85.7%, compared to 42.9% in the 14-day group. Among the 13 patients with IDH1/2 mutations, 8 (61.5%) achieved MRD negativity. Literature review supports IDH1/2 mutations as identifying a favorable population for VEN+AZA therapy, associated with deep molecular responses.Conclusion:IDH1/2 mutations showed a positive trend toward MRD negativity following VEN+AZA therapy, although statistical significance was not reached (P?= 0.098). The 28-day regimen may be associated with a higher rate of MRD negativity. In this exploratory analysis with limited statistical power, patients with IDH mutations demonstrated a higher MRD negativity rate, suggesting that achieving MRD negativity could be considered a therapeutic goal in this patient population.

  Key words: IDH1/2 mutation; Acute myeloid leukemia; Venetoclax; Azacitidine; Measurable residual disease; Unfit for intensive chemotherapy

  Submit time: 3 April 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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