PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.
Abstract
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.
Type
Journal articleSubject
AnimalsHumans
Lymphoma, B-Cell
Antibodies, Monoclonal
Programmed Cell Death 1 Receptor
B7-H1 Antigen
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https://hdl.handle.net/10161/19336Published Version (Please cite this version)
10.1182/blood-2017-07-740993Publication Info
Xu-Monette, Zijun Y; Zhou, Jianfeng; & Young, Ken H (2018). PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood, 131(1). pp. 68-83. 10.1182/blood-2017-07-740993. Retrieved from https://hdl.handle.net/10161/19336.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Zijun Yidan Xu-Monette
Assistant Professor in Pathology
My research efforts have been focused on identifying prognostic and therapeutic biomarkers
in B-cell lymphoma. My research interests also include investigation of molecular
and immune mechanisms underlying the poor clinical outcomes of lymphoma, the pathogenesis
and evolution of drug resistant clones, and development of novel therapies for aggressive
B-cell lymphoma.
Ken H Young
Professor of Pathology
I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic
diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue,
spleen and pre-malignant hematologic conditions. Another area of interest is blood
cancer classification with molecular and genetic profiling. In my research program,
we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers,
and novel therapeutic strategies in lymphoma, myeloma and leukemia. In
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