Details

Autor(en) / Beteiligte

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

Titel

Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma

Ist Teil von

• Journal of clinical oncology, 2018-04, Vol.36 (10), p.942-950

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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-β2-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 β2-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.