Abstract 5792: Characterization of the tumor microenvironment in a relapsed refractory multiple myeloma patient undergoing daratumumab therapy
Authors: Siobhan B. Cashman, Aruna Ayer, Teresa Swift
Journal: Cancer Research (2025)

Abstract Multiple Myeloma (MM), a hematological malignancy, is characterized by the clonal proliferation of plasma cells in the bone marrow (BM), which serves as the tumor microenvironment. Despite recent advancements in MM treatment, many patients experience disease progression after multiple therapies. Daratumumab, a human IgG1 monoclonal antibody targeting CD38, has emerged as a breakthrough in the treatment of MM, including in cases of relapsed and refractory MM. However, MM remains incurable and therefore understanding the impact of daratumumab on immune microenvironment may enable the development of better-targeted therapies. This study represents a detailed case of a 45-year-old female with relapsed refractory MM undergoing daratumumab therapy. BM aspirates were collected from the patient before treatment initiation &amp; 7-days post final infusion. To delineate the early cellular and molecular changes induced by daratumumab within the TME, we employed flow cytometry and single-cell whole transcriptome sequencing with CITE-seq. Flow cytometry was used to assess the changes in cell populations within the TME, particularly focusing on CD8+ T cells and NK cells. Single-cell RNA sequencing enabled the high-resolution analysis of both transcriptomic and surface protein changes within individual cells. Post-infusion, we observed an increased percentage in CD8+ T effector memory (TEM) cell subsets accompanied by a corresponding decrease in effector memory expressing CD45-RA (TEMRA). Single-cell sequencing identified heightened activity in the interferon and TNF pathways. Additionally, there was an increased percentage of granzyme B expressing CD8+ T cells. Although we observed no significant change in the percentage of NK cells post-infusion, we did note an increased percentage of CD56BrightCD16- NK and CD3+CD8+CD56+ NK-T-like subsets as well as decreased CD57+ terminally differentiated NK cells. We observed increased transcript expression of CD160 (encoding the activating receptor CD160/NK1) in the post-daratumumab NK cell cluster. Further, we noted increased activity in the NFκB pathway in post-treatment NK cells. This case study underscores daratumumab’s rapid impact on the immune cell landscape within the BM TME. By combining flow cytometry with single-cell whole transcriptome sequencing and CITE-seq this study provided a comprehensive view of the effect of therapy on the MM TME. Through CITE-seq, we identified the dynamic changes in the BM immune cell landscape and captured protein expression patterns specific to targeted cell populations. This approach allowed us to link surface marker expression with gene expression profiles, enabling a comprehensive analysis of the BM TME. For Research-Use Only. Not for use in diagnostic or therapeutic procedures. BD and the BD Logo are trademarks of Becton, Dickinson and Company. © 2024 BD. All rights reserved. NPM-5206 Citation Format: Siobhan B. Cashman, Aruna Ayer, Teresa Swift. Characterization of the tumor microenvironment in a relapsed refractory multiple myeloma patient undergoing daratumumab therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5792.