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 Maxted AnsellKazunobu Kato, Benedetto Farsaci, Anne Sumbul, Philippe Armand, Donna S. Neuberg, Geraldine S. Pinkus, Azra H. Ligon, Scott J. Rodig, Margaret A. Shipp

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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.

Original languageEnglish (US)
Pages (from-to)942-950
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number10
DOIs
StatePublished - Apr 1 2018

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Reed-Sternberg Cells
Major Histocompatibility Complex
Hodgkin Disease
Ligands
Disease-Free Survival
Antigen Presentation
Death Domain Receptors
Stem Cell Transplantation
Fluorescence In Situ Hybridization
Immunity
Immunohistochemistry
Biopsy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma. / Roemer, Margaretha G.M.; Redd, Robert A.; Cader, Fathima Zumla; Pak, Christine J.; Abdelrahman, Sara; Ouyang, Jing; Sasse, Stephanie; Younes, Anas; Fanale, Michelle; Santoro, Armando; Zinzani, Pier Luigi; Timmerman, John; Collins, Graham P.; Ramchandren, Radhakrishnan; Cohen, Jonathon B.; De Boer, Jan Paul; Kuruvilla, John; Savage, Kerry J.; Trneny, Marek; Ansell, Stephen Maxted; Kato, Kazunobu; Farsaci, Benedetto; Sumbul, Anne; Armand, Philippe; Neuberg, Donna S.; Pinkus, Geraldine S.; Ligon, Azra H.; Rodig, Scott J.; Shipp, Margaret A.

In: Journal of Clinical Oncology, Vol. 36, No. 10, 01.04.2018, p. 942-950.

Research output: Contribution to journalArticle

Roemer, MGM, Redd, RA, Cader, FZ, Pak, CJ, Abdelrahman, S, Ouyang, J, Sasse, S, Younes, A, Fanale, M, Santoro, A, Zinzani, PL, Timmerman, J, Collins, GP, Ramchandren, R, Cohen, JB, De Boer, JP, Kuruvilla, J, Savage, KJ, Trneny, M, Ansell, SM, Kato, K, Farsaci, B, Sumbul, A, Armand, P, Neuberg, DS, Pinkus, GS, Ligon, AH, Rodig, SJ & Shipp, MA 2018, 'Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma', Journal of Clinical Oncology, vol. 36, no. 10, pp. 942-950. https://doi.org/10.1200/JCO.2017.77.3994
Roemer, Margaretha G.M. ; Redd, Robert A. ; Cader, Fathima Zumla ; Pak, Christine J. ; Abdelrahman, Sara ; Ouyang, Jing ; Sasse, Stephanie ; Younes, Anas ; Fanale, Michelle ; Santoro, Armando ; Zinzani, Pier Luigi ; Timmerman, John ; Collins, Graham P. ; Ramchandren, Radhakrishnan ; Cohen, Jonathon B. ; De Boer, Jan Paul ; Kuruvilla, John ; Savage, Kerry J. ; Trneny, Marek ; Ansell, Stephen Maxted ; Kato, Kazunobu ; Farsaci, Benedetto ; Sumbul, Anne ; Armand, Philippe ; Neuberg, Donna S. ; Pinkus, Geraldine S. ; Ligon, Azra H. ; Rodig, Scott J. ; Shipp, Margaret A. / Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 10. pp. 942-950.
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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.",
author = "Roemer, {Margaretha G.M.} and Redd, {Robert A.} and Cader, {Fathima Zumla} and Pak, {Christine J.} and Sara Abdelrahman and Jing Ouyang and Stephanie Sasse and Anas Younes and Michelle Fanale and Armando Santoro and Zinzani, {Pier Luigi} and John Timmerman and Collins, {Graham P.} and Radhakrishnan Ramchandren and Cohen, {Jonathon B.} and {De Boer}, {Jan Paul} and John Kuruvilla and Savage, {Kerry J.} and Marek Trneny and Ansell, {Stephen Maxted} and Kazunobu Kato and Benedetto Farsaci and Anne Sumbul and Philippe Armand and Neuberg, {Donna S.} and Pinkus, {Geraldine S.} and Ligon, {Azra H.} and Rodig, {Scott J.} and Shipp, {Margaret A.}",
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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 Maxted

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 - 2018/4/1

Y1 - 2018/4/1

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.

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U2 - 10.1200/JCO.2017.77.3994

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