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Accepted Articles of Congress

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  • Histone Deacetylase Inhibitor Sensitivity in EZH2-Mutant Diffuse Large B-Cell Lymphoma: A Systematic Review

  • Alireza Pourrahim,1,* Mohammad Mahdi Pourrahim,2 Omid Raiesi,3 Alireza Vasiee,4
    1. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    2. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    3. Omid Raiesi
    4. Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran


  • Introduction: EZH2 gain-of-function mutations drive aberrant histone methylation and oncogenic transcriptional programs in diffuse large B-cell lymphoma (DLBCL). Histone deacetylase inhibitors (HDACis) may counteract EZH2-mediated epigenetic repression, but the magnitude of clinical benefit in EZH2-mutant DLBCL remains unclear.
  • Methods: We searched PubMed, EMBASE, Web of Science, and Scopus up to June 2025 for clinical studies evaluating HDACi therapy (e.g., vorinostat, panobinostat, romidepsin) in adult DLBCL patients stratified by EZH2 mutation status. Inclusion criteria were prospective trials or cohort studies reporting response rates, survival outcomes, or adverse events in EZH2-mutant cohorts. Two reviewers independently screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias tool for interventional studies and the Newcastle–Ottawa Scale for observational cohorts. Discrepancies were resolved by consensus.
  • Results: Four studies encompassing 278 DLBCL patients (114 EZH2-mutant; median follow-up 16 months) met inclusion criteria. Across EZH2-mutant cohorts, the pooled overall response rate was 57.9% (95% CI 49.2–66.6; I² = 21%), with a complete response rate of 24.6% (95% CI 18.0–31.2). Median progression-free survival was 10.8 months (95% CI 9.4–12.2) and median overall survival was 22.7 months (95% CI 20.1–25.3). The hazard ratio for progression or death in EZH2-mutant versus wild-type cohorts was 0.68 (95% CI 0.52–0.89; p = 0.006). Treatment-related grade ≥3 adverse events occurred in 18.3% of EZH2-mutant patients (95% CI 14.0–22.6).
  • Conclusion: EZH2-mutant DLBCL patients demonstrate substantial sensitivity to HDACi therapy, with ORR nearing 60%, durable median PFS of nearly 11 months, and an acceptable safety profile. These findings support further exploration of HDACis, alone or in combination, as targeted therapies in EZH2-driven DLBCL and warrant randomized trials stratified by mutation status.
  • Keywords: EZH2 mutation; diffuse large B-cell lymphoma; histone deacetylase inhibitor

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