DETERMINATION OF THE CELL OF ORIGIN (COO) in LDCGB

Overview

This is a prospective, multicenter study, without any therapeutic intervention that will consist of the analysis of the results of the determination of the COO of all the patients diagnosed with LDCGB in the Spanish hospitals of GELTAMO that adhere to the project. The determination of the COO will be carried out prospectively at the Genomic Unit of the Hospital Clínic de Barcelona (IDIBAPS), where the histological samples of the patients will be sent for this purpose. The main study variable will be the description of the COO (germ-center origin \[GCB\], activated \[ABC\], NOT DETERMINABLE, NOT VALUABLE)

Diffuse large B-cell lymphoma (LDCGB) is the most frequent form of lymphoma in Western countries, accounting for between 30 and 50% of all of them, and represents the paradigm of aggressive lymphoma (1). The current treatment is based on immunochemotherapy, that is, the combination of polychemotherapy (most commonly the CHOP regimen) with an anti-CD20 monoclonal antibody (rituximab). With this therapeutic approach a high proportion of patients are cured, but still 25-35% of them either do not respond to treatment or eventually relapse into the disease (2). New therapies in the experimental phase include other monoclonal antibodies of different specificity and small molecules with a target action. LDCGB is actually heterogeneous and includes at least two subtypes depending on the cell of origin (COO): those related to a germline center B cell (GCB) and those similar to a post-germline center or activated B cell (ABC). Such groups show important biological, but also clinical and prognostic differences (3). Thus, ABC-type LDCGBs are more aggressive and patients have a worse prognosis. Recent data indicate that COO is also of therapeutic importance: thus, ABC-type LDCGBs would be particularly sensitive to NFkB and certain kinase inhibitors (4). Thus, the determination of COO now basically academic, is going to be a conventional diagnostic procedure in the coming years. The determination of COO was initially carried out by a gene expression profiling (GEP) technique with frozen material (3). This technique is not realistic in the field of clinical care. Different immunohistochemical algorithms to mimic PEG results in paraffin tissue face great doubts about their reliability and, in fact, cannot be considered conventional (5). More recently, a NanoString technique has been implemented to determine the COO in paraffin tissue with an excellent correlation with PEG results (6). This technique has been used in the context of clinical trials, but no information is available in the general population setting. Precisely the aim of the present project is to apply the NanoString technique to the determination of COO of patients with LDCGB diagnosed during 2018 and 2019 in the Spanish centers associated to the cooperative group GELTAMO.