BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.

Follicular Lymphoma Clinical Trial

— BCL6-RINHL  

Official title:

Study of Clinical, Histological, Immunohistochemical and Molecular Impact of BCL6 Gene Rearrangement in Most Prevalent Non-Hodgkin Lymphomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06424379
• Other study ID #: 69HCL24_0515
• Status: Active, not recruiting
• Start date: January 1, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.

Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.

A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.

FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.

MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.

Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: June 30, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 100 Years

Eligibility

Inclusion Criteria:

• Diagnostic of non-Hodgkin's lymphoma at anatomy and cytology department of Lyon Sud hospital

• Rearrangement of the BCL6 gene detected by FISH analysis

• Diagnostic of the disease between january 2016 and december 2023

Exclusion Criteria:

• Patients diagnosed with primary cutaneous centrofollicular B lymphoma, composite lymphoma, anaplastic B lymphoma or primary B lymphoma of the mediastinum.

• Presence of a rearrangement of the BLC2 gene or the CMYC gene in FISH

• Presence of a non-significant BCL6 gene rearrangement (<5% of rearranged cells)

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Marginal Zone Lymphoma
• Non Hodgkin Lymphoma

Intervention

Other:
• Histopathological analysis
Morphological analysis will include the description of architectural patterns and cytological features on formalin-fixed and paraffin-embedded (FFPE) tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of immunohistochemical staining will be analyzed including CD20, CD3, CD10, Bcl-6, Bcl-2, CD5, CD23, CD38, MUM1, Ig kappa, Ig lambda, MEF2B, LMO2, MNDA, IRTA1, P53, CMYC and Ki67 . /MIB1. Diffuse large B-cells lymphomas will be classified into two distinct subgroups: centro-germinative (GC) and non-centro-germinative (nGC), using the Hans algorithm.

Genetic:
• Molecular analysis
Next-generation sequencing (NGS) analysis will be performed on FFPE tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of 73 genes dedicated to lymphoma diagnosis determined by a consensus of French Lysa experts will be used. The identification of genetic variants will be followed by the attribution of pathogenicity class in accordance with the guidelines for validation of NGS-based oncology panels. RNA extraction will classify DLBCLs into two distinct subgroups: germinal-centre B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL).

Locations

Country	Name	City	State
France	Hopital Lyon Sud - HCL	Pierre-Bénite

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of LF and MZL with BCL6-R.	An examination of morphological attributes, including tissue architecture and cellular patterns will be performed on LF and MZL with BCL6-R. An extended immunohistochemical staining panel employing incorporated novel centro-germinative markers (LMO2 and MEF2B) and recently identified MZL-specific markers (IRTA1 and MNDA) is planned.	The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
Primary	Comparison of LF and MZL with BCL6-R.	Fluorescence in situ hybridization (FISH) will be employed for cytogenetic evaluation to detect BCL2 and BCL6 gene rearrangements. In parallel, targeted next-generation sequencing (NGS) analysis will enable genetic variant detection.	The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year