Exploring the Clinical Impact of MYC Aberrations and Their Relationship With Microenvironment in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma

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.

• Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology [Time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)]
• Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology [Time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)]
• Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology [Time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)]
• Identify putative prognostic and predictive biomarkers related to the lymphoma microenvironment [Time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)]
• Analyze the impact of the type of therapy, standard or intensified (with or without autotransplantation), on the outcome in the different subgroups of patients [Time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)]
• Assess the risk of central nervous system (CNS) recurrence and the impact of prophylaxis performed with intrathecal chemotherapy vs methotrexate intravenous [Time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)]