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

Margaretha G. M. Roemer, Robert A. Redd, Fathima Zumla Cader, Christine J. Pak, Sara Abdelrahman, Jing Ouyang, Stephanie Sasse, Anas Younes, Michelle Fanale, Armando Santoro, Pier Luigi Zinzani, John Timmerman, Graham P. Collins, Radhakrishnan Ramchandren, Jonathon B. Cohen, Jan Paul de Boer, John Kuruvilla, Kerry J. Savage, Marek Trneny, Stephen AnsellKazunobu Kato, Benedetto Farsaci, Anne Sumbul, Philippe Armand, Donna S. Neuberg, Geraldine S. Pinkus, Azra H. Ligon, Scott J. Rodig, Margaret A. Shipp

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)942-950
JournalJournal of Clinical Oncology
Issue number10
Publication statusPublished - 2018

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