PhD Scientific Days 2025

Pathological and Oncological Sciences I.

Investigation of the interrelation between EZH2 mutations and prognosis in follicular lymphoma – results of a national multicentre cohort study

Name of the presenter

Hanza Richard

Institute/workplace of the presenter

HCEMM-HAS-SU Momentum Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University

Authors

Mr. Richard Hanza¹

1: HCEMM-HAS-SU Momentum Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University

Text of the abstract

Introduction: Follicular lymphoma (FL) is the most common indolent B-cell lymphoma with heterogeneous prognosis. The survival of FL improved significantly due to the combinations of bendamustine-rituximab (BR) and rituximab, cyclophosphamide, hydroxidaunorubicine, vincristine and prednisolone (R-CHOP) as frontline treatments, however currently there is a lack of reliable prognostic markers. The role of EZH2 mutations, which are therapeutic targets in relapsing/refractory FL, gained substantial interest in risk assessment, but based on the current literature, their prognostic significance dubious.
Aims: Our aim was to investigate the prognostic value of EZH2 mutations in a registry-based multicentric Hungarian cohort study and to elucidate the prognostic role of EZH2 mutations in FL with performing an additional meta-analysis on previously published data.
Methods: 167 patients, diagnosed between 2008 and 2021 were involved from national hematological centres. We assessed their EZH2 status using digital droplet PCR and also their clinicopathological parameters were summarised. Statistical analysis was performed by RStudio (v. 4.4.0) software and Kaplan-Meier analysis, log-rank test and Cox regression was performed. Literature was summarised by meta-analysis using the site metaanalysisonline.com.
Results: 28,7% (48/167) of patients harboured EZH2 mutations. There was no significant difference in progression free survival (PFS) in the whole cohort (n=167, p=0.43), BR-treated (n=77, p=0.83) and R-CHOP treated (n=90, p=0.31) cohorts stratified by EZH2 status. The PFS of EZH2 mutated patients stratified by therapy also did not differ significantly (n=48, p=0.35). According to the univariate analysis only medium (HR: 2.46, p=0.03) and high (HR: 2.44, p=0.02) FLIPI risk proved to be significant markers. BR and R-CHOP treated patients were not prone to significantly higher risk in PFS according to the meta-analysis (n=417, ORR=0.95, p=0.75 vs. n=457, ORR=0.72, p=0.43) when stratified by EZH2 status.
Conclusions and funding: Based on our results, using EZH2 mutation status in the prognosis assessment of FL patients is not supported during first line immunochemotherapy. Supported by the 2024-2.1.1-EKÖP-2024-00004 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research Development and Innovation Fund.