期刊
BLOOD
卷 131, 期 1, 页码 68-83出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2017-07-740993
关键词
-
类别
资金
- National Institutes of Health, National Cancer Institute [R01CA138688, R01CA187415, 1RC1CA146299]
- National Cancer Institute
- National Institutes of Health [P50CA136411, P50CA142509]
- MD Anderson Cancer Center Support Grant [CA016672]
- University of Texas MD Anderson Cancer Center Institutional Research and Development Fund
- Gundersen Lutheran Medical Foundation Award
- Hagemeister Lymphoma Foundation Award
- University Cancer Foundation via the Sister Institution Network Fund at The University of Texas MD Anderson Cancer Center
- Key Program of National Natural Science Funds of China [81230052, 81630006]
- Roche Molecular System
- Gilead Sciences
- Seattle Genetics
- Dai Sanyo
- Adaptive Biotechnology
- Incyte Pharmaceutical
- HTG Molecular Diagnostics
- Perfectgen Diagnostics
Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1(+) tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1(+) T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据