Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma
| Autor: | Brian Fox, Ethan G. Thompson, Greg Pietz, Kathryn Newhall, Wilbert B. Copeland, Mary H. Young, Elizabeth Whalen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Durvalumab
Combination therapy Science Receptors Antigen T-Cell B7-H1 Antigen Article Interferon-gamma Antineoplastic Agents Immunological Immune system Tumor Microenvironment medicine Humans Multiple myeloma Dexamethasone Tumor microenvironment Multidisciplinary Sequence Analysis RNA business.industry Antibodies Monoclonal medicine.disease Pomalidomide Thalidomide Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cancer research Medicine Drug Therapy Combination Bone marrow Multiple Myeloma business Biomarkers medicine.drug |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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