Contributions
Abstract: EP799
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin's lymphoma, accounting for 25% of all newly diagnosed lymphomas in Russia. The clinical course of the disease is variable and associated with tumor morphology: the prognosis for grade 1-2 and 3A is better than for grade 3B and for transformation into aggressive lymphomas (Fig. 1). The variability of the clinical course is also observed among indolent FL (grade 1-2 and 3A). The variability of the disease can be explained by the pathogenetic mechanisms (“linear” and divergent pathways) of the development of the tumor cell, which are confirmed by the detected genetic markers. EZH2 is an early marker of FL and its changes confirm the «linear“ pathway of tumor cell development. Today the pathogenetic aspects of FL are not fully understood and the data are contradictory.
Aims
To determine the mutational status of the EZH2 gene in patients with indolent FL, to compare the results obtained with the immunomorphological and cytogenetic characteristics of the tumor; to determine predictive value.
Methods
A prospective comparative search study conducted from January, 2020 to December, 2020 at the National Research Center for Hematology (Moscow) included 64 patients (35 men and 29 women, with a median age of 53 years) with newly diagnosed FL. All 64 biopsies taken before therapy administration were investigated for the mutational status of EZH2 gene exon 16 (Sanger sequencing) and for the rearrangement of the BCL2 gene (karyotyping and FISH). All patients received anthracycline-containing regimens with rituximab (R-CHOP / R-EPOCH). Molecular, immunomorphological and cytogenetic data were compared blindly with the outcome of immunochemotherapy treatment.
Results
Mutations of EZH2 gene (mutEZH2) were detected in 10/64 (16%) of cases. In the mutEZH2 group of patients grade 1-2 of FL was diagnosed in 4/10 cases, and grade 3A - in 6 out of 10 cases. Rearrangement of the BCL2 was found in 1-2 grade group in 3/4 cases, in 3A grade - in 3/6 cases. Adverse events (early relapse/progression/death from progression were determined in 4/10 (40%) patients and only in cases with EZH2 mutations and without BCL2 gene rearrangement. There were no deaths in cases with both EZH2 mutations and BCL2 gene rearrangement.
Wild type EZH2 gene status (wtEZH2) was shown for 54/64 (84%) cases. In this group grade 1-2 FL was diagnosed in 26/54 (48%) cases, and grade 3A – in 28/54 (52%). BCL2 gene rearrangement was detected in 19/22 (86%) grade 1-2 FL cases, and in 14/25 (56%) grade 3A cases. Adverse events in the group without EZH2 mutations were found in 20/54(37%), and were twice as common in the absence of BCL2 gene rearrangement (16% versus 82% in grade 1-2, and 36% versus 100% in grade 3A). Deaths from progression were observed in 12/54 (22%) patients.
Conclusion
EZH2 gene mutations were detected in 16% of cases and were found equally in grade 1-2 and 3A groups of FL patients. FL cases with both EZH2 mutations and BCL2 rearrangement are characterized by a long persistently recurrent course. FL cases with wild type EZH2 gene and without BCL2 gene rearrangement are associated with a high risk of transformation into DLBCL and high mortality.
Keyword(s): EZH2, Follicular lymphoma, Prognosis
Abstract: EP799
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin's lymphoma, accounting for 25% of all newly diagnosed lymphomas in Russia. The clinical course of the disease is variable and associated with tumor morphology: the prognosis for grade 1-2 and 3A is better than for grade 3B and for transformation into aggressive lymphomas (Fig. 1). The variability of the clinical course is also observed among indolent FL (grade 1-2 and 3A). The variability of the disease can be explained by the pathogenetic mechanisms (“linear” and divergent pathways) of the development of the tumor cell, which are confirmed by the detected genetic markers. EZH2 is an early marker of FL and its changes confirm the «linear“ pathway of tumor cell development. Today the pathogenetic aspects of FL are not fully understood and the data are contradictory.
Aims
To determine the mutational status of the EZH2 gene in patients with indolent FL, to compare the results obtained with the immunomorphological and cytogenetic characteristics of the tumor; to determine predictive value.
Methods
A prospective comparative search study conducted from January, 2020 to December, 2020 at the National Research Center for Hematology (Moscow) included 64 patients (35 men and 29 women, with a median age of 53 years) with newly diagnosed FL. All 64 biopsies taken before therapy administration were investigated for the mutational status of EZH2 gene exon 16 (Sanger sequencing) and for the rearrangement of the BCL2 gene (karyotyping and FISH). All patients received anthracycline-containing regimens with rituximab (R-CHOP / R-EPOCH). Molecular, immunomorphological and cytogenetic data were compared blindly with the outcome of immunochemotherapy treatment.
Results
Mutations of EZH2 gene (mutEZH2) were detected in 10/64 (16%) of cases. In the mutEZH2 group of patients grade 1-2 of FL was diagnosed in 4/10 cases, and grade 3A - in 6 out of 10 cases. Rearrangement of the BCL2 was found in 1-2 grade group in 3/4 cases, in 3A grade - in 3/6 cases. Adverse events (early relapse/progression/death from progression were determined in 4/10 (40%) patients and only in cases with EZH2 mutations and without BCL2 gene rearrangement. There were no deaths in cases with both EZH2 mutations and BCL2 gene rearrangement.
Wild type EZH2 gene status (wtEZH2) was shown for 54/64 (84%) cases. In this group grade 1-2 FL was diagnosed in 26/54 (48%) cases, and grade 3A – in 28/54 (52%). BCL2 gene rearrangement was detected in 19/22 (86%) grade 1-2 FL cases, and in 14/25 (56%) grade 3A cases. Adverse events in the group without EZH2 mutations were found in 20/54(37%), and were twice as common in the absence of BCL2 gene rearrangement (16% versus 82% in grade 1-2, and 36% versus 100% in grade 3A). Deaths from progression were observed in 12/54 (22%) patients.
Conclusion
EZH2 gene mutations were detected in 16% of cases and were found equally in grade 1-2 and 3A groups of FL patients. FL cases with both EZH2 mutations and BCL2 rearrangement are characterized by a long persistently recurrent course. FL cases with wild type EZH2 gene and without BCL2 gene rearrangement are associated with a high risk of transformation into DLBCL and high mortality.
Keyword(s): EZH2, Follicular lymphoma, Prognosis