A Molecular Classifier Increased the Accuracy of Lymphoma Diagnosis By Expert Pathologists in the Diffuse Large B-Cell Lymphoma Gained Trial from the Lysa

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.3495-3495
• Main Authors: Moslemi, Amine, Bobée, Victor, Blanc-Durand, Paul, Drieux, Fanny, Desmots-Loyer, Fabienne, Briere, Josette, Casasnovas, Olivier, Canioni, Danielle, Ghesquieres, Herve, Gaulard, Philippe, Oberic, Lucie, Damotte, Diane, Morschhauser, Franck, Martin, Antoine, Tilly, Hervé, Thieblemont, Catherine, Ribrag, Vincent, Hermine, Olivier, Haioun, Corinne, Lamy, Thierry, Fest, Thierry, Jardin, Fabrice, Le Gouill, Steven, Itti, Emmanuel, Ruminy, Philippe, Molina, Thierry Jo
• Format: Article
• Language: English
• Subjects: Life Sciences
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-152144

Introduction We (Bobée et al, 2020) have recently described a new molecular classifier combining gene expression profiling of 137 genes and machine learning able to diagnose B-cell lymphomas. As this tool can be easily performed from formalin fixed paraffin embedded tissue, we proposed to evaluate how it may be useful after the process of central review by expert pathologists in a LYSA diffuse large B-cell lymphoma (DLBCL) clinical trial, the GAINED trial (Le Gouill et al, 2021). Methods The GAINED trial was a multicenter randomized phase 3 trial comparing obinutuzumab to rituximab followed by a PET-driven consolidation in patients with DLBCL. Histological inclusion criteria were : DLBCL, high grade B-cell lymphoma double/triple hit (DH/TH) or high grade NOS. 670 patients were included and 646 underwent a central review of the biopsy by at least two LYSA pathologists. The central review performed immunostaining of full slides by anti-CD20, CD5, CD10, BCL6, MUM1, MYC, BCL2 if sufficient material was available as well as RNA extraction for the molecular classifier, the nanostring Lymph2CX and DNA extraction for targeted NGS. The molecular classifier was able to deliver 8 different signatures: DLBCL GCB, DLBCL ABC, primary mediastinal large B-cell lymphoma (PMBL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma/lymphoplasmacytic lymphoma, CLL/lymphocytic Lymphoma, T-cell rich signature. We compared classification by the histopathology review and by the molecular classifier. Discordant cases were reviewed both by two histopathologists (JB, TJM) and the molecular biologist (PR) and a reconciliation diagnosis was proposed Results The central histopathological review alone identified 580 patients with DLBCL or high grade B-cell lymphoma and 40 patients with a lymphoma subtype not eligible for the trial. Among the 470 patients evaluated by the molecular classifier, the reconciliation diagnosis identified 292 DLBCL NOS with 40 associated with a small B-cell component, 13 High grade DH/TH, 9 high grade NOS, 109 PMBL, 16 T-cell rich large B-cell Lymphoma (TCRBCL), 5 DLBCL EBV+ NOS. 29 cases did not fit with inclusion criteria and were mainly FL (3A or 3B), MCL, Nodular lymphocyte Predominant Hodgkin Lymphoma (NLPHL). Among them, the classifier helped to identify one case of CD5- MCL initially diagnosed as DLBCL with CD5- marginal zone lymphoma as well as one case of CD10+ follicular T-cell lymphoma (T-cell rich signature with Rho A mutati