Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Conditions
Keywords
Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, MYC, BCL2, BCL6, Double Hit, Triple Hit, lymphoma micro-environment
Brief summary
This is a observational, retrospective and prospective study designed to assess the potential correlations between MYC alterations, lymphoma mutational landscape and functional immune contextures in Diffuse Large B-cell Lymphoma or High-Grade B-cell Lymphoma
Detailed description
Diffuse large B-cell lymphomas (DLBCL) and high-grade B-cell lymphomas (HGBCL) are a group of heterogeneous diseases representing more than a third of lymphomas in adults. 5-years overall survival of patients affected by DLBCL and HGBCL is around 70-60% and efficient prognostic markers are warranted to improve patients' survival by better tailored therapeutical approaches. Genetic rearrangements of the MYC gene occur in 5-10% of DLBCL at diagnosis, and the presence of double translocations involving both MYC and BCL2 (double-hit, DH), associated or not with BCL6 (triple-hit, TH) translocation, is associated with unfavorable prognostic impact. Intensification of treatment compared to standard chemotherapy (R-CHOP) appears to reduce the risk of recurrence in patients with DH or TH lymphomas, but a survival advantage has not been demonstrated. Numerical changes in MYC (gain of copy number, GCN) may also affect the outcome of patients with DLBCL, but their prognostic relevance and the benefit of treatment intensification is still controversial. Additionally, novel scientific evidence indicates a contribution of lymphoma micro-environment (LME) in disease genomic subtype and patient prognosis. We aimed this study at investigating potential biological links between MYC aberrations, lymphoma mutational landscape and functional immune contextures in DLBCL and HGBCL.
Interventions
None listed
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of nodal and extranodal Diffuse Large B Cell Lymphoma, High Grade B Cell Lymphomas (including low-grade transformed lymphomas; double and triple hit; 11q aberration; not otherwise specified) after 1st January 2019 * Presence of one MYC translocation or gain of copies (GCN: \> 3 copies in more than 30% of the nuclei) or amplification evaluated by FISH * Availability of immunohistochemical analysis of CD10, Bcl6, MUM1, Bcl2, Myc, Ki67 * Have received curative treatment (e.g. R-CHOP, R DA EPOCH, intensified Burkitt like chemotherapies) as first-line therapy * Histological material of adequate size and quality to perform histological review with any additional investigations (immunohistochemistry, FISH and other molecular analysis). A FFPE block must be provided for patient enrollment. * Age between 18 and 79 years
Exclusion criteria
* Primary lymphomas of the central nervous system, plasmablastic lymphoma, Burkitt's lymphoma, primary mediastinal B lymphoma * Have received palliative treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the histopathological, genetic, clinical characteristics and outcome of patients with DLBCL or HGBCL with MYC rearrangements or GCN (alone or in association with BCL2 and BCL6) treated with curative intent therapy | The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) | Comparison of Progression Free Survival (PFS) according to genetic subgroups with or without intensified treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology | The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) | % of patients with presence of MYC, BCL2 and/or BCL6 translocation evaluated by FISH |
| Identify putative prognostic and predictive biomarkers related to the lymphoma microenvironment | The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) | Correlation between the microenvironment signature and patient Overall Survival (OS) |
| Analyze the impact of the type of therapy, standard or intensified (with or without autotransplantation), on the outcome in the different subgroups of patients | The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) | Progression Free Survival comparison in the different subgroups of lymphomas and according to the type of treatment received |
| Assess the risk of central nervous system (CNS) recurrence and the impact of prophylaxis performed with intrathecal chemotherapy vs methotrexate intravenous | The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) | Progression Free Survival comparison in the different subgroups of lymphomas and according to the type of treatment received |
Countries
Italy
Contacts
Primary ContactUffici Studi FIL
Backup ContactUffici Studi FIL
Outcome results
None listed