Mixed Molecular Clinical Index (MMCI) in Diffuse Large B-cell Lymphoma (DLBCL)

Condition(s) studied

Investigational drug(s) / intervention(s)

Prospective cohort: Immunohistochemical determinations: Cell of Origin (COO) (according with Hans algorithm), evaluation of Cluster of Differentiation (CD) (CD20, CD5, CD10), Bcl6, Bcl2 (cut off\>50%), MUM1/IRF4, c-myc (cut off\>40%) and Ki67, FISH for c-myc and if rearranged for Bcl2 e Bcl6. mRNA expression by Nanostring Single cell analysis Immune checkpoint expression Proteomic analysis Metabolic analysis Radiomic analysis

Retrospective cohort: Immunohistochemical determinations: Cell of Origin (COO) (according with Hans algorithm), evaluation of Cluster of Differentiation (CD) (CD20, CD5, CD10), Bcl6, Bcl2 (cut off\>50%), MUM1/IRF4, c-myc (cut off\>40%) and Ki67, FISH for c-myc and if rearranged for Bcl2 e Bcl6. mRNA expression by Nanostring Single cell analysis Immune checkpoint expression Proteomic analysis Metabolic analysis Radiomic analysis

Study summary

This is a prospective and retrospective observational study. The primary objective is to identify new prognostic biomarkers for DLBCL patients in terms of progression-free survival (PFS) and able to add predictive capacity to recognized important clinical factors.

The secondary objectives are:

* to identify new biomarkers associated with overall survival (OS) and objective response rate (ORR)
* to characterize tissue and circulating immune microenvironment of DLBCL patients by bulk and single cell transcriptomics;
* to assess the correlation between the expression of immune checkpoint genes and mRNA signature;
* to describe the mutational status of a panel of genes relevant to DLBCL pathogenesis;.
* to assess the correlation between protein expression, mutational status and the messenger RNA (mRNA) signature.
* to investigate the association between radiomic features obtained from PET images and patient and tumour characteristics and clinical outcomes (PFS, OS, ORR).

For each enrolled patient, immunohistochemical determinations will be performed: Cell of origin (COO) (Germinal Cell -GC- or activated B-cell - ABC- type according with Hans algorithm ), evaluation of cluster of differentiation antigen 20 (CD20), cluster of differentiation antigen 5 (CD5), cluster of differentiation antigen 10 (CD10), Bcl6, Bcl2 (cut off\>50%), Multiple Myeloma 1 / Interferon Regulatory Factor 4 protein (MUM1/IRF4), c-myc (cut off\>40%) and Ki67, fluorescence in situ hybridization (FISH) for c-myc and if rearranged, for Bcl2 e Bcl6 ). Moreover, paraffin embedded (FFPE) tumor specimens will be collected for RNA extraction and mRNA expression mutational and proteomics analysis, centralized at IRST-IRCCS.

Eligibility

Primary outcome measure(s)

• identification of new prognostic biomarkers — 3 years
  To identify new prognostic biomarkers for DLBCL patients that combined to clinical factors (IPI) are able to create a MMCI, predictive in terms of progression-free survival (PFS) of DLBCL patients.

Trial sites (4)

More Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS trials in Italy

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