PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

Xu-Monette, Zijun Y

Zhou, Jianfeng

Young, Ken H

2019-09-21T21:27:14Z

2019-09-21T21:27:14Z

2018-01

2019-09-21T21:27:13Z

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.

blood-2017-07-740993

0006-4971

1528-0020

https://hdl.handle.net/10161/19336

eng

American Society of Hematology

Blood

10.1182/blood-2017-07-740993

Animals

Humans

Lymphoma, B-Cell

Antibodies, Monoclonal

Programmed Cell Death 1 Receptor

B7-H1 Antigen

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

Journal article

Xu-Monette, Zijun Y|0000-0002-7615-3949

Young, Ken H|0000-0002-5755-8932

68

83

1

School of Medicine

Duke

Pathology

Clinical Science Departments

Published

131