$Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma$
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Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma

Abstract This study sought to understand how the programmed death ligand 1 (PD-L1) inhibitor durvalumab and the immunomodulatory agent pomalidomide regulate immune cell activation and function in patients with relapsed/refractory (RR) multiple myeloma (MM). Immunologic changes in peripheral blood an...

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Autores principales:	Mary H. Young, Greg Pietz, Elizabeth Whalen, Wilbert Copeland, Ethan Thompson, Brian A. Fox, Kathryn J. Newhall
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12984849fdd84a40badc86697ac75613
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spelling	oai:doaj.org-article:12984849fdd84a40badc86697ac756132021-12-02T16:27:50ZImmunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma10.1038/s41598-021-95902-x2045-2322https://doaj.org/article/12984849fdd84a40badc86697ac756132021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95902-xhttps://doaj.org/toc/2045-2322Abstract This study sought to understand how the programmed death ligand 1 (PD-L1) inhibitor durvalumab and the immunomodulatory agent pomalidomide regulate immune cell activation and function in patients with relapsed/refractory (RR) multiple myeloma (MM). Immunologic changes in peripheral blood and bone marrow of patients treated with durvalumab as monotherapy or in combination with pomalidomide with/without dexamethasone were characterized by assessing subsets of immune cells and gene signatures to understand the immunomodulatory effect of the treatment. Soluble PD-L1 levels were elevated at screening in patients with RRMM but did not correlate with response to durvalumab combination therapy. Immune cell subsets were increased in peripheral blood during treatment with durvalumab and pomalidomide, and combination therapy induced significant gene expression changes in the MM tumor microenvironment versus durvalumab alone. Estimation of cell populations based on RNA sequencing data revealed increased monocytes, neutrophils, and natural killer cells with the combination therapy, but not with durvalumab alone. Additionally, multiplex immunofluorescence of bone marrow demonstrated that immune populations were different in responders versus nonresponders to durvalumab plus pomalidomide with dexamethasone therapy. Overall, durvalumab effectively blocked soluble PD-L1; however, durvalumab monotherapy was not associated with immunologic changes, which were observed with combination therapy.Mary H. YoungGreg PietzElizabeth WhalenWilbert CopelandEthan ThompsonBrian A. FoxKathryn J. NewhallNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mary H. Young Greg Pietz Elizabeth Whalen Wilbert Copeland Ethan Thompson Brian A. Fox Kathryn J. Newhall Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
description	Abstract This study sought to understand how the programmed death ligand 1 (PD-L1) inhibitor durvalumab and the immunomodulatory agent pomalidomide regulate immune cell activation and function in patients with relapsed/refractory (RR) multiple myeloma (MM). Immunologic changes in peripheral blood and bone marrow of patients treated with durvalumab as monotherapy or in combination with pomalidomide with/without dexamethasone were characterized by assessing subsets of immune cells and gene signatures to understand the immunomodulatory effect of the treatment. Soluble PD-L1 levels were elevated at screening in patients with RRMM but did not correlate with response to durvalumab combination therapy. Immune cell subsets were increased in peripheral blood during treatment with durvalumab and pomalidomide, and combination therapy induced significant gene expression changes in the MM tumor microenvironment versus durvalumab alone. Estimation of cell populations based on RNA sequencing data revealed increased monocytes, neutrophils, and natural killer cells with the combination therapy, but not with durvalumab alone. Additionally, multiplex immunofluorescence of bone marrow demonstrated that immune populations were different in responders versus nonresponders to durvalumab plus pomalidomide with dexamethasone therapy. Overall, durvalumab effectively blocked soluble PD-L1; however, durvalumab monotherapy was not associated with immunologic changes, which were observed with combination therapy.
format	article
author	Mary H. Young Greg Pietz Elizabeth Whalen Wilbert Copeland Ethan Thompson Brian A. Fox Kathryn J. Newhall
author_facet	Mary H. Young Greg Pietz Elizabeth Whalen Wilbert Copeland Ethan Thompson Brian A. Fox Kathryn J. Newhall
author_sort	Mary H. Young
title	Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
title_short	Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
title_full	Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
title_fullStr	Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
title_full_unstemmed	Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
title_sort	immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/12984849fdd84a40badc86697ac75613
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Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma

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