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Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed

Margaretha G M Roemer1, Robert A Redd1, Fathima Zumla Cader1

  • 1Margaretha G.M. Roemer, Robert A. Redd, Fathima Zumla Cader, Christine J. Pak, Sara Abdelrahman, Jing Ouyang, Philippe Armand, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Geraldine S. Pinkus, Azra H. Ligon, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer, VU University Medical Center; Jan Paul De Boer, Antoni van Leeuwenhoek Hospital, Lunenburg Phase I/II Consortium, Amsterdam, the Netherlands; Stephanie Sasse, University Hospital of Cologne, Cologne, Germany; Anas Younes, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Fanale, University of Texas MD Anderson Cancer Center, Houston, TX; Armando Santoro, Humanitas University, Rozzano, Milan; Pier Luigi Zinzani, University of Bologna, Bologna, Italy; John Timmerman, University of California, Los Angeles Medical Center, Los Angeles, CA; Graham P. Collins, Churchill Hospital, Oxford, United Kingdom; Radhakrishnan Ramchandren, Barbara Ann Karmanos Cancer Institute, Detroit, MI; Jonathon B. Cohen, Emory University, Atlanta, GA; John Kuruvilla, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Kerry J. Savage, British Columbia Cancer Agency Center for Lymphoid Cancer, Vancouver, British Columbia, Canada; Marek Trneny, Charles University in Prague, General University Hospital in Prague, Prague, Czech Republic; Stephen Ansell, Mayo Clinic, Rochester, MN; and Kazunobu Kato, Benedetto Farsaci, and Anne Sumbul, Bristol-Myers Squibb, Princeton, NJ.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|February 3, 2018
PubMed

Insights

Genetically driven programmed death-ligand 1 (PD-L1) expression and MHC class II positivity on Hodgkin Reed-Sternberg cells predict favorable outcomes in classic Hodgkin lymphoma patients treated with PD-1 blockade.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Hodgkin Reed-Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) employ immune evasion strategies, including 9p24.1 alterations and altered antigen presentation.
  • Despite PD-1 blockade efficacy, HRS cells often show deficient MHC class I expression, posing a question about treatment sensitivity.

Purpose of the Study:

  • To investigate the predictive value of 9p24.1 alterations, PD-L1, and antigen presentation pathway components for PD-1 blockade response in relapsed/refractory cHL.
  • To assess sensitivity to nivolumab (anti-PD-1) in the context of these biomarkers.

Main Methods:

  • Archival tumor biopsies from cHL patients treated with nivolumab in the CheckMate 205 trial were analyzed.
  • Fluorescence in situ hybridization assessed 9p24.1 copy gain; immunohistochemistry evaluated PD-L1, MHC class I, and MHC class II expression on HRS cells.
  • Correlations between biomarkers, clinical response, and progression-free survival (PFS) were determined.

Main Results:

  • Higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells correlated with superior PFS.
  • HRS cell expression of β2-microglobulin and MHC class I did not predict complete remission or PFS.
  • MHC class II expression on HRS cells predicted complete remission and, in specific patient subgroups, prolonged PFS.

Conclusions:

  • Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are promising predictors of favorable outcomes with PD-1 blockade in cHL.
  • Clinical responses to nivolumab in cHL are not contingent on HRS cell MHC class I expression.

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