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 ORCID: 0000-0003-1709-9492, 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 ORCID: 0000-0001-8275-2561, Sumbul, Anne, Armand, Philippe, Neuberg, Donna S., Pinkus, Geraldine S., Ligon, Azra H., Rodig, Scott J. and Shipp, Margaret A. (2018). Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma. J. Clin. Oncol., 36 (10). S. 942 - 954. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

PurposeHodgkin 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.MethodsHRS 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 components2-microglobulin, MHC class I, and MHC class IIby immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade.ResultsPatients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of 2-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.ConclusionGenetically 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. (C) 2018 by American Society of Clinical Oncology

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Roemer, Margaretha G. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Redd, Robert A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cader, Fathima ZumlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pak, Christine J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdelrahman, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ouyang, JingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sasse, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Younes, AnasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fanale, MichelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Santoro, ArmandoUNSPECIFIEDorcid.org/0000-0003-1709-9492UNSPECIFIED
Zinzani, Pier LuigiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timmerman, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collins, Graham P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramchandren, RadhakrishnanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cohen, Jonathon B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Boer, Jan PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuruvilla, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Savage, Kerry J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trneny, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ansell, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kato, KazunobuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farsaci, BenedettoUNSPECIFIEDorcid.org/0000-0001-8275-2561UNSPECIFIED
Sumbul, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Armand, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuberg, Donna S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pinkus, Geraldine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ligon, Azra H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodig, Scott J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shipp, Margaret A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-190022
DOI: 10.1200/JCO.2017.77.3994
Journal or Publication Title: J. Clin. Oncol.
Volume: 36
Number: 10
Page Range: S. 942 - 954
Date: 2018
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REED-STERNBERG CELLS; T-CELLS; BRENTUXIMAB VEDOTIN; ANALYSIS REVEALS; PD-1 BLOCKADE; TUMOR-CELLS; MELANOMA; THERAPY; TRANSPLANTATION; IMMUNOTHERAPYMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19002

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