Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation.

Autor:	Hodkinson BP; Oncology Translational Research, Janssen Research & Development, Spring House, PA 19477, United States., 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; Department of Hematology, University Hospital Vall d'Hebron, Department of Medicine. Universitat Autònoma de Barcelona (UAB), Vall d'Hebron Institut of Oncology (VHIO), Barcelona, Spain., Ben-Yehuda D; Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel., Avivi I; Department of Hematology and Bone Marrow Transplantation, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv 6997801, Israel., Forslund A; Oncology Biomarkers, Bristol-Myers Squibb, Lawrenceville, NJ 08543, United States., Özcan M; Department of Hematology, Ankara University School of Medicine, Ankara 06100, Turkey., Alvarez J; Oncology Translational Research, Janssen Research & Development, Spring House, PA 19477, United States., Ceulemans R; Translational Medicine, Janssen Research & Development, Beerse 2340, Belgium., Fourneau N; Translational Medicine, Janssen Research & Development, Beerse 2340, Belgium., Younes A; Lymphoma Department, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States., Balasubramanian S; Oncology Translational Research, Janssen Research & Development, Spring House, PA 19477, United States. Electronic address: sbalas14@ITS.JNJ.com.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2021 Jan; Vol. 14 (1), pp. 100977. Date of Electronic Publication: 2020 Dec 06.
DOI:	10.1016/j.tranon.2020.100977
Abstrakt:	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. Competing Interests: Declaration of Competing Interest A. Younes received research funding from Novartis, Janssen, and Curtis and honoraria from Bayer, Merck, Bristol Myers Squibb, Celgene, Incyte, Janssen, Sanofi, Seattle Genetics, and Takeda Millennium. W. Jurczak has served as a consultant or in an advisory role for Janssen-Cilag, Acerta Pharma, Sandoz-Novartis, Celltrion, MEI Pharma, Roche, and Gilead Sciences and has received research funding from Janssen-Cilag, Acerta Pharma, Merck, Gilead Sciences, TG Therapeutics, Pfizer, Incyte, Bayer HealthCare Pharmaceuticals, Sandoz-Novartis, Roche, Celltrion, Takeda Pharmaceuticals, Affimed Therapeutics, and Epizyme. M. Özcan has received research funding from Archigen, AbbVie, Novartis, Bayer, Roche, MSD, Janssen, Celgene, and Takeda and honoraria and travel funding from Takeda, Bristol Myers Squibb, JAZZ, Sanofi, Abdi İbrahim, and Roche. JD Brody received research funding from Janssen, Merck, Bristol Myers Squibb, Seattle Genetics, Takeda, Kite, Acerta, Celgene, and Morphosys. A. Forslund is an employee of Bristol Myers Squibb and owns stock in the company. B. Hodkinson, M. Schaffer, N. Fourneau, J. Alvarez, R. Ceulemans, and S. Balasubramanian are employees of the Janssen Pharmaceutical Companies of Johnson & Johnson. S. Balasubramanian owns stock in Pharmacyclics/AbbVie. C. Carpio, I. Avivi, and D. Ben-Yehuda have nothing to disclose. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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