Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance.

Autor:	Laurent C; CHU Toulouse, IUCT Oncopole, Centre de Recherche en Cancerologie de Toulouse Inserm UMR 1037,, Toulouse, France., Trisal P; Bristol Myers Squibb, Summit, New Jersey, United States., Tesson B; LYSARC, France., Seth S; Bristol Myers Squibb, Cambridge, Massachusetts, United States., Beyou A; CIML, marseille, France., Roulland S; CIML, marseille, France., Lesne B; LYSARC, The Lymphoma Academic Research Organization, Pierre-Bénite, France., Van Acker N; CHU Toulouse, IUCT Oncopole, Centre de Recherche en Cancerologie de Toulouse Inserm UMR 1037,, Toulouse, France., Cerapio JP; Centre de Recherches en Cancérologie de Toulouse INSERM U1037, Toulouse, France., Chartier L; LYSARC, PIERRE-BENITE, France., Guille A; Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, Inserm U1068, CNRS UMR7258, Aix-Marseille University, UM105, 13009 Marseille, France., Stokes ME; Bristol-Myers Squibb, Summit, New Jersey, United States., Huang CC; Bristol Myers Squibb, Summit, New Jersey, United States., Huet S; Centre hopitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France., Gandhi AK; Bristol-Myers Squibb, Summit, New Jersey, United States., Morschhauser F; Hopital Claude Huriez, France., Xerri L; Institut Paoli-Calmettes, AMU, CRCM, INSERM, Marseille, France.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Oct 07. Date of Electronic Publication: 2024 Oct 07.
DOI:	10.1182/blood.2024024496
Abstrakt:	A robust prognostic and biological classification for newly diagnosed follicular lymphoma (FL) using molecular profiling remains challenging. FL tumors from patients treated in the RELEVANCE trial with rituximab-chemotherapy (R-chemo) or rituximab-lenalidomide (R2) were analyzed using RNA-sequencing, DNA-sequencing, immunohistochemistry (IHC) and/or fluorescence in situ hybridization. Unsupervised gene clustering identified two gene expression signatures (GS) enriched with normal memory (MEM) B-cells and germinal center (GC) B-cells signals, respectively. These two GS were combined into a 20-genes predictor (FL20) to classify patients into MEM-like (n=160) or GC-like (n=164) subtypes, which also displayed different mutational profiles. In the R-chemo arm, MEM-like patients had significantly shorter progression free survival (PFS) than GC-like patients (HR=2.13; p=0.0023), and this prognostic correlation remained significant in a multivariable model including FLIPI (p=0.005). In the R2 arm, both subtypes had comparable PFS, demonstrating a R2 benefit over R-chemo for MEM-like patients (HR=0.54; p=0.011). The prognostic value of FL20 was validated in an independent FL cohort with R-chemo treatment (GSE119214 (n=137)). An IHC algorithm (FLCM) using FOXP1, LMO2, CD22 and MUM1 antibodies was developed with significant prognostic correlation with FL20 in a training set of RELEVANCE (n=264) patients, which was then validated in a different set of patients (n=116). These data indicate that FL tumors can be classified into MEM-like and GC-like subtypes that are biologically distinct and clinically different in risk profile. The FLCM assay can be used in routine clinical practice to identify MEM-like FL patients who might benefit from therapies other than R-chemo, such as the R2 combination. ClinicalTrials.gov identifier: RELEVANCE: NCT01476787 and NCT01650701 INTRODUCTION. (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu