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.

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