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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2021-08-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-95902-x |
id |
doaj-12984849fdd84a40badc86697ac75613 |
---|---|
record_format |
Article |
spelling |
doaj-12984849fdd84a40badc86697ac756132021-08-15T11:26:03ZengNature Publishing GroupScientific Reports2045-23222021-08-0111111410.1038/s41598-021-95902-xImmunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myelomaMary H. Young0Greg Pietz1Elizabeth Whalen2Wilbert Copeland3Ethan Thompson4Brian A. Fox5Kathryn J. Newhall6Bristol Myers SquibbBristol Myers SquibbBristol Myers SquibbBristol Myers SquibbBristol Myers SquibbBristol Myers SquibbBristol Myers SquibbAbstract 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.https://doi.org/10.1038/s41598-021-95902-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mary H. Young Greg Pietz Elizabeth Whalen Wilbert Copeland Ethan Thompson Brian A. Fox Kathryn J. Newhall |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-95902-x |
work_keys_str_mv |
AT maryhyoung immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma AT gregpietz immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma AT elizabethwhalen immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma AT wilbertcopeland immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma AT ethanthompson immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma AT brianafox immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma AT kathrynjnewhall immunomodulationbydurvalumabandpomalidomideinpatientswithrelapsedrefractorymultiplemyeloma |
_version_ |
1721206821572575232 |