Revised International Prognostic Index and genetic alterations are associated with early failure to R-CHOP in patients with diffuse large B-cell lymphoma.

Adult Aged Antineoplastic Combined Chemotherapy Protocols / adverse effects Biomarkers, Tumor Biopsy Cyclophosphamide / adverse effects DNA Copy Number Variations DNA Mutational Analysis Doxorubicin / adverse effects Female Gene Expression Profiling Genetic Predisposition to Disease Genetic Variation Humans In Situ Hybridization, Fluorescence Lymphoma, Large B-Cell, Diffuse / diagnosis Male Middle Aged Neoplasm Grading Neoplasm Staging Odds Ratio Prednisone / adverse effects Prognosis Rituximab / adverse effects Treatment Failure Treatment Outcome Vincristine / adverse effects

Diffuse large B-cell lymphoma early failure to therapy gene expression genetic alterations prognostic factors

Journal

British journal of haematology

ISSN: 1365-2141

Titre abrégé: Br J Haematol

Pays: England

ID NLM: 0372544

Informations de publication

Date de publication:
02 2022

Historique:

revised: 26 08 2021

received: 14 06 2021

accepted: 12 09 2021

pubmed: 12 10 2021

medline: 15 2 2022

entrez: 11 10 2021

Statut: ppublish

Résumé

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) cases have a poor outcome. Here we analysed clinico-biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, mutational status of 106 genes was studied by targeted next-generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39. Ninety-seven cases (26%) were identified as EF and showed significantly shorter overall survival (OS). Patients with B symptoms, advanced stage, high levels of serum lactate dehydrogenase (LDH) or β2-microglobulin, low lymphocyte/monocyte ratio and higher Revised International Prognostic Index (R-IPI) scores, as well as those with BCL2 rearrangements more frequently showed EF, with R-IPI being the most important in logistic regression. Mutations in NOTCH2, gains in 5p15·33 (TERT), 12q13 (CDK2), 12q14·1 (CDK4) and 12q15 (MDM2) showed predictive importance for EF independently from R-IPI. GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over-representation of gene sets related to extra-cellular matrix and tumour microenvironment.

Identifiants

DOI: 10.1111/bjh.17858 PMID: 34632572

pubmed: 34632572

doi: 10.1111/bjh.17858

doi:

Substances chimiques

Biomarkers, Tumor 0

R-CHOP protocol 0

Rituximab 4F4X42SYQ6

Vincristine 5J49Q6B70F

Doxorubicin 80168379AG

Cyclophosphamide 8N3DW7272P

Prednisone VB0R961HZT

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

589-598

Informations de copyright

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