期刊
JOURNAL OF CLINICAL ONCOLOGY
卷 36, 期 10, 页码 942-+出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2017.77.3994
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资金
- National Institutes of Health [NIH R01CA061026]
- NIH [5P30 CA006516]
- Miller Family Fund
- Bristol-Myers Squibb
- NATIONAL CANCER INSTITUTE [P30CA008748, P30CA006516, R01CA161026] Funding Source: NIH RePORTER
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
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