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

Frontiers in Immunology

Immunology

Ravi Vij¹  Elisabeth Wassner-Fritsch²  Tina G. Nielsen²  Rajan Sareen³  Aparna Raval³  Habib Hamidi³  Luciano J. Costa⁴  Selma Bekri⁵  Hearn J. Cho⁶  Sandy Wong⁷  Natalia Neparidze⁸ 

[1] Division of Oncology, Washington University, St. Louis, MO, United States;F. Hoffmann-La Roche Ltd., Basel, Switzerland;Genentech Inc., South San Francisco, CA, United States;O’Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, United States;Tisch Cancer Institute, Icahn School of Medicine at Mt. Sinai, New York, NY, United States;Tisch Cancer Institute, Icahn School of Medicine at Mt. Sinai, New York, NY, United States;The Multiple Myeloma Research Foundation (MMRF), Norwalk, CT, United States;University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, United States;Yale School of Medicine, New Haven, CT, United States;

关键词: atezolizumab;    daratumumab;    multiple myeloma;    biomarkers;    tumor microenvironment, multi-omics;   

DOI  :  10.3389/fimmu.2023.1085893

 received in 2022-10-31, accepted in 2023-05-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Wong, Hamidi, Costa, Bekri, Neparidze, Vij, Nielsen, Raval, Sareen, Wassner-Fritsch and Cho