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Translating the Biology of Diffuse Large B-cell Lymphoma Into Treatment.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is characterized by clinical and molecular heterogeneity; however, this heterogeneity is rarely taken into account by standard-of-care treatment approaches. While the disease was traditionally classified based on transcriptome signatures purporting the tumor cell of origin, recent classification systems have further differentiated these subtypes into clusters based on molecular and genetic features. Alongside a better understanding of the biology of the disease and the signaling pathways involved, emerging therapeutic agents may be better aimed at attacking distinct disease subsets. It is hoped that molecular subtyping at diagnosis will allow patients to be allocated to the appropriate treatment that targets their specific disease subtype, thus advancing the promise of precision medicine in lymphoma, an approach that is most needed. For high-risk disease subsets, this is particularly important, and much research is still needed to develop agents effective in this population. Here, we review recent advances in DLBCL biology and how they can be translated into clinical care.

SUBMITTER: Danilov AV

PROVIDER: S-EPMC8842307 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Translating the Biology of Diffuse Large B-cell Lymphoma Into Treatment.

Danilov Alexey V AV Magagnoli Massimo M Matasar Matthew J MJ

The oncologist 20220201 1

Diffuse large B-cell lymphoma (DLBCL) is characterized by clinical and molecular heterogeneity; however, this heterogeneity is rarely taken into account by standard-of-care treatment approaches. While the disease was traditionally classified based on transcriptome signatures purporting the tumor cell of origin, recent classification systems have further differentiated these subtypes into clusters based on molecular and genetic features. Alongside a better understanding of the biology of the dise ...[more]

PMID: 35305092

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Project description:Objectives/hypothesisThis study utilizes a large population national database to comprehensively analyze prognosticators and overall survival (OS) outcomes of varying treatment modalities in a large cohort of sinonasal diffuse large B-cell lymphoma (SN-DLBCL) patients.Study designRetrospective database study.MethodsThe National Cancer Database was queried for all SN-DLBCL cases diagnosed from 2004 to 2015. Kaplan-Meier log-rank test determined differences in OS based on clinical covariates. Cox proportional-hazards analysis was used to determine clinical and sociodemographic covariates predictive of mortality.ResultsA total of 2,073 SN-DLBCL patients were included, consisting of 48% female with a mean age of 66.0 ± 16.2 years. Overall, 82% of patients were Caucasian, 74% had early-stage disease, and 49% had primary tumors in the paranasal sinuses. Early-stage patients were more likely to receive multi-agent chemoradiotherapy compared to multi-agent chemotherapy alone (P < .001). Multivariable Cox proportional-hazards analysis revealed chemoradiotherapy to confer significantly greater OS improvements than chemotherapy alone (hazard ratio [HR]: 0.61; P < .001). However, subset analysis of late-stage patients demonstrated no significant differences in OS between these treatment modalities (P = .245). On multivariable analysis of chemotherapy patients treated post-2012, immunotherapy (HR = 0.51; P = .024) demonstrated significant OS benefits. However, subset analysis showed no significant advantage in OS with administering immunotherapy for late-stage patients (P = .326). Lastly, for all patients treated post-2012, those receiving immunotherapy had significantly improved OS compared to those not receiving immunotherapy (P < .001).ConclusionsTreatment protocol selection differs between early- and late-stage SN-DLBCL patients. Early-stage patients receiving chemotherapy may benefit from immunotherapy as part of their treatment paradigm.Level of evidence3 Laryngoscope, 131:E2727-E2735, 2021.

Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) constitutes 30% of all non-Hodgkin's lymphomas. It can present as a nodal disease or as an extra nodal disease. Based on the site of origin, extra nodal DLBCL (EN-DLBCL) may have a distinct clinical outcome. Apart from the site of origin, factors including demographics, stage, and presence of any other primary malignancy also affect the outcome. The purpose of our study was to characterize prognostically distinct groups based on the site of presentation of EN-DLBCL.MethodsWe used 18 registries in Surveillance, Epidemiology, and End Results database to identify the patients with EN-DLBCL for 2000 - 2015 with last follow-up till December 31, 2018. A total of 30,290 EN-DLBCL patients were selected and categorized based on 13 broad sites grouping. Demographic variables were summarized. We did overall survival analysis with univariate and multivariate Cox-proportional hazard modeling. Short-term survival trend was calculated as well.ResultsThe percentage of EN-DLBCL of all DLBCLs is 34.48%. EN-DLBCL was comparatively seen more in males (54.94%) and non-Hispanic whites (71.52%). In terms of clinical characteristics, patients with EN-DLBCL were mostly diagnosed at age ≥ 60 years (66.11%), early stage (69.33%), and presentation as first primary cancer (81.89%). A higher risk of mortality was seen in non-Hispanic black (hazard ratio (HR) 1.36), with late age of onset (HR 2.69), late stage at presentation (HR 1.42), and with history of other malignancy (HR 1.29). Compared to the intestinal tract, the risk of overall mortality was higher in individuals with involvement of nervous system (HR 1.85), pancreas and hepatobiliary system (HR 1.22), and respiratory system (HR 1.18) and the best outcomes were seen in heart and mediastinal site (HR 0.58) of DLBCL.ConclusionBased upon our population-based study, we conclude that primary site of presentation of EN-DLBCL is an important prognostic factor with significant difference in survival based on histological and epidemiological characteristics.

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Translating the Biology of Diffuse Large B-cell Lymphoma Into Treatment.

Publications

Translating the Biology of Diffuse Large B-cell Lymphoma Into Treatment.

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