Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma

• Type of Material: Article
• Authors: Margaretha G.M. Roemer, Dana Farber Cancer Institute; Robert A. Redd, Dana Farber Cancer Institute; Fathima Zumia Cader, Dana Farber Cancer Institute; Christine J. Pak, Dana Farber Cancer Institute; Sara Abdelrahman, Dana Farber Cancer Institute; Jing Ouyang, Dana Farber Cancer Institute; Stephanie Sasse, University Hospital of Cologne; Anas Younes, Memorial Sloan Kettering Cancer Center; Michelle Fanale, University of Texas MD Anderson Cancer Center; Armando Santoro, Humanitas University; Pier Luigi Zinzani, University of Bologna; John Timmerman, University of California Los Angeles; Graham P. Collins, Churchill Hospital; Radhikrishnan Ramchandren, Barbara Ann Karmanos Cancer Institute; Jonathon B Cohen, Emory University; Jan Paul De Boer, Antoni van Leeuwenhoek Hospital; John Kuruvilla, Princess Margaret Cancer Centre; Kerry J. Savage, British Columbia Cancer Agency; Marek Trneny, Charles University Prague; Stephen Ansell, Mayo Clinic; Kazunobu Kato, Bristol Myers Squibb; Benedetto Farsaci, Bristol Myers Squibb; Anne Sumbul, Bristol Myers Squibb; Philippe Armand, Dana Farber Cancer Institute; Donna S. Neuberg, Dana Farber Cancer Institute; Geraldine S. Pinkus, Brigham and Women's Hospital; Azra H. Ligon, Brigham and Women's Hospital; Scott J. Rodig, Brigham and Women's Hospital; Margaret A. Shipp, Dana Farber Cancer Institute
• Language: English
• Date: 2018-04-01
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2018 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2017.77.3994
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 36
• Issue: 10
• Start Page: 942
• End Page: +
• Grant/Funding Information: Funded by National Institutes of Health Grants No. NIH R01CA061026 (M.A.S.) and NIH 5P30 CA006516 (R.A.R.), the Miller Family Fund (M.A.S.), and Bristol-Myers Squibb (S.J.R. and M.A.S.).
• Keywords: PD-1 BLOCKADE; Life Sciences & Biomedicine; THERAPY; IMMUNOTHERAPY; REED-STERNBERG CELLS; T-CELLS; MELANOMA; Oncology; TRANSPLANTATION; Science & Technology; immunohistochemistry; BRENTUXIMAB VEDOTIN; ANALYSIS REVEALS; TUMOR-CELLS
• Research Categories: Health Sciences, Oncology; Health Sciences, Immunology; Health Sciences, Rehabilitation and Therapy

Abstract

Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components-b2-microglobulin, MHC class I, and MHC class II-by immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. Results Patients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of b2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a . 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.