dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Hodkinson, Brendan P. |
dc.contributor.author | Schaffer, Michael |
dc.contributor.author | Brody, Joshua D. |
dc.contributor.author | Carpio Segura, Cecilia Carmen |
dc.contributor.author | Ben-Yehuda, Dina |
dc.contributor.author | Jurczak, Wojciech |
dc.date.accessioned | 2021-06-14T12:41:37Z |
dc.date.available | 2021-06-14T12:41:37Z |
dc.date.issued | 2021-01 |
dc.identifier.citation | Hodkinson 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.issn | 1936-5233 |
dc.identifier.uri | https://hdl.handle.net/11351/6069 |
dc.description | Biomarkers; Ibrutinib; Non-hodgkin's lymphoma |
dc.description.abstract | We 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.iso | eng |
dc.publisher | Elsevier |
dc.relation.ispartofseries | Translational Oncology;14(1) |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.source | Scientia |
dc.subject | Limfomes |
dc.subject | Medicaments antineoplàstics |
dc.subject | Marcadors bioquímics |
dc.subject.mesh | Lymphoma |
dc.subject.mesh | Drug Therapy, Combination |
dc.subject.mesh | Biomarkers |
dc.title | Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1016/j.tranon.2020.100977 |
dc.subject.decs | linfoma |
dc.subject.decs | farmacoterapia combinada |
dc.subject.decs | biomarcadores |
dc.relation.publishversion | https://www.sciencedirect.com/science/article/pii/S1936523320304691 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 33395752 |
dc.identifier.wos | 000604582000003 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |