Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma Journal Article


Authors: Roemer, M. G. M.; Redd, R. A.; Cader, F. Z.; Pak, C. J.; Abdelrahman, S.; Ouyang, J.; Sasse, S.; Younes, A.; Fanale, M.; Santoro, A.; Zinzani, P. L.; Timmerman, J.; Collins, G. P.; Ramchandren, R.; Cohen, J. B.; De Boer, J. P.; Kuruvilla, J.; Savage, K. J.; Trneny, M.; Ansell, S.; Kato, K.; Farsaci, B.; Sumbul, A.; Armand, P.; Neuberg, D. S.; Pinkus, G. S.; Ligon, A. H.; Rodig, S. J.; Shipp, M. A.
Article Title: Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma
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. © 2018 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 10
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-04-01
Start Page: 942
End Page: 950
Language: English
DOI: 10.1200/jco.2017.77.3994
PROVIDER: scopus
PMCID: PMC5877802
PUBMED: 29394125
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Anas Younes
    199 Younes