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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorHodkinson, Brendan P.
dc.contributor.authorSchaffer, Michael
dc.contributor.authorBrody, Joshua D.
dc.contributor.authorJurczak, Wojciech
dc.contributor.authorCarpio Segura, Cecilia Carmen
dc.contributor.authorBen-Yehuda, Dina
dc.date.accessioned2021-06-14T12:41:37Z
dc.date.available2021-06-14T12:41:37Z
dc.date.issued2021-01
dc.identifier.citationHodkinson BP, Schaffer M, Brody JD, Jurczak W, Carpio C, Ben-Yehuda D, et al. Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter’s transformation. Transl Oncol. 2021 Jan;14(1):100977.
dc.identifier.issn1936-5233
dc.identifier.urihttp://hdl.handle.net/11351/6069
dc.descriptionBiomarkers; Ibrutinib; Non-hodgkin's lymphoma
dc.description.abstractWe analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter's transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5%] vs. 3/16 [18.8%]; p = 0.065; complete response 37.5% vs. 0%; p = 0.028). Overall response rates for patients with WES and GEP data, respectively, were: DLBCL (38.5% and 29.6%); FL (46.2% and 43.5%); RT (76.5% and 81.3%). In DLBCL, WES analyses demonstrated that mutations in RNF213 (40.0% vs. 6.2%; p = 0.055), KLHL14 (30.0% vs. 0%; p = 0.046), and LRP1B (30.0% vs. 6.2%; p = 0.264) were more frequent in responders. No responders had mutations in EBF1, ADAMTS20, AKAP9, TP53, MYD88 , or TNFRSF14 , while the frequency of these mutations in nonresponders ranged from 12.5% to 18.8%. In FL and RT, genes with different mutation frequencies in responders versus nonresponders were: BCL2 (75.0% vs. 28.6%; p = 0.047) and ROS1 (0% vs. 50.0%; p = 0.044), respectively. Per GEP, the most upregulated genes in responders were LEF1 and BTLA (overall), and CRTAM (germinal center B-cell–like DLBCL). Enriched pathways were related to immune activation in responders and resistance-associated proliferation/replication in nonresponders. This preliminary work may help to generate hypotheses regarding genetically defined subsets of DLBCL, FL, and RT patients most likely to benefit from ibrutinib plus nivolumab.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesTranslational Oncology;14(1)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectLimfomes
dc.subjectMedicaments antineoplàstics
dc.subjectMarcadors bioquímics
dc.subject.meshLymphoma
dc.subject.meshDrug Therapy, Combination
dc.subject.meshBiomarkers
dc.titleBiomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.tranon.2020.100977
dc.subject.decslinfoma
dc.subject.decsfarmacoterapia combinada
dc.subject.decsbiomarcadores
dc.relation.publishversionhttps://www.sciencedirect.com/science/article/pii/S1936523320304691
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Hodkinson BP, Schaffer M] Oncology Translational Research, Janssen Research & Development, Spring House, PA 19477, United States. [Brody JD] Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. [Jurczak W] Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, 31-115, Poland. [Carpio C] Servei d’Hematologia i hemoteràpia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Ben-Yehuda D] Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
dc.identifier.pmid33395752
dc.identifier.wos000604582000003
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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