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Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM

Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase...

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Autores principales: Wong, Sandy, Hamidi, Habib, Costa, Luciano J., Bekri, Selma, Neparidze, Natalia, Vij, Ravi, Nielsen, Tina G., Raval, Aparna, Sareen, Rajan, Wassner-Fritsch, Elisabeth, Cho, Hearn J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408441/
https://www.ncbi.nlm.nih.gov/pubmed/37559718
http://dx.doi.org/10.3389/fimmu.2023.1085893
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author Wong, Sandy
Hamidi, Habib
Costa, Luciano J.
Bekri, Selma
Neparidze, Natalia
Vij, Ravi
Nielsen, Tina G.
Raval, Aparna
Sareen, Rajan
Wassner-Fritsch, Elisabeth
Cho, Hearn J.
author_facet Wong, Sandy
Hamidi, Habib
Costa, Luciano J.
Bekri, Selma
Neparidze, Natalia
Vij, Ravi
Nielsen, Tina G.
Raval, Aparna
Sareen, Rajan
Wassner-Fritsch, Elisabeth
Cho, Hearn J.
author_sort Wong, Sandy
collection PubMed
description Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma.
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spelling pubmed-104084412023-08-09 Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM Wong, Sandy Hamidi, Habib Costa, Luciano J. Bekri, Selma Neparidze, Natalia Vij, Ravi Nielsen, Tina G. Raval, Aparna Sareen, Rajan Wassner-Fritsch, Elisabeth Cho, Hearn J. Front Immunol Immunology Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma. Frontiers Media S.A. 2023-07-25 /pmc/articles/PMC10408441/ /pubmed/37559718 http://dx.doi.org/10.3389/fimmu.2023.1085893 Text en Copyright © 2023 Wong, Hamidi, Costa, Bekri, Neparidze, Vij, Nielsen, Raval, Sareen, Wassner-Fritsch and Cho https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wong, Sandy
Hamidi, Habib
Costa, Luciano J.
Bekri, Selma
Neparidze, Natalia
Vij, Ravi
Nielsen, Tina G.
Raval, Aparna
Sareen, Rajan
Wassner-Fritsch, Elisabeth
Cho, Hearn J.
Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
title Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
title_full Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
title_fullStr Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
title_full_unstemmed Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
title_short Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
title_sort multi-omic analysis of the tumor microenvironment shows clinical correlations in ph1 study of atezolizumab +/- soc in mm
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408441/
https://www.ncbi.nlm.nih.gov/pubmed/37559718
http://dx.doi.org/10.3389/fimmu.2023.1085893
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