TY - JOUR
T1 - Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma
AU - Roemer, Margaretha G. M.
AU - Redd, Robert A.
AU - Cader, Fathima Zumla
AU - Pak, Christine J.
AU - Abdelrahman, Sara
AU - Ouyang, Jing
AU - Sasse, Stephanie
AU - Younes, Anas
AU - Fanale, Michelle
AU - Santoro, Armando
AU - Zinzani, Pier Luigi
AU - Timmerman, John
AU - Collins, Graham P.
AU - Ramchandren, Radhakrishnan
AU - Cohen, Jonathon B.
AU - de Boer, Jan Paul
AU - Kuruvilla, John
AU - Savage, Kerry J.
AU - Trneny, Marek
AU - Ansell, Stephen
AU - Kato, Kazunobu
AU - Farsaci, Benedetto
AU - Sumbul, Anne
AU - Armand, Philippe
AU - Neuberg, Donna S.
AU - Pinkus, Geraldine S.
AU - Ligon, Azra H.
AU - Rodig, Scott J.
AU - Shipp, Margaret A.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045065481&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29394125
U2 - https://doi.org/10.1200/JCO.2017.77.3994
DO - https://doi.org/10.1200/JCO.2017.77.3994
M3 - Article
C2 - 29394125
SN - 0732-183X
VL - 36
SP - 942
EP - 950
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 10
ER -