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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Tuesday, January 3, 2023
Changes in the genome and immune microenvironment composition of patients with newly diagnosed multiple myeloma who receive daratumumab, carfilzomib, lenalidomide, and dexamethasone (DKRd) therapy may be related to failure to establish sustained measurable residual disease (MRD) negativity, according to Eileen M. Boyle, MD, MSc, of New York University Langone Health, and colleagues. The results of this study, which suggest that Fc-mediated antibody effector function, inflammation reversal, and T-cell oligoclonality can influence the achievement of sustained MRD negativity, were presented during the 2022 American Society of Hematology (ASH) Annual Meeting and Exhibition (Abstract 100).
5'single-cell RNA sequencing as well as T-cell receptor and surface protein markers (CITEseq) capture were performed on a total of 148,280 cells from 17 patients at induction of DKRd and 18 patients at the end of induction. Data from 27 identified cell types were analyzed for changes in gene expression. Healthy bone marrow cells from the Human Cell Atlas were integrated with the data for comparison. Additionally, T-cell receptor sequencing and analysis were performed on 22,882 alpha-beta clonotypes.
Marked changes in the microenvironment occurred between diagnosis and the end of induction, including a significant association between the achievement of sustained MRD negativity and an expansion of activated CD56-bright natural killer (NK) cells (chi-squared = 4, P = .044). The investigators also found resident-like macrophages, indicating a potential link between certain “immune hot” tumors and poor treatment response. They propose that despite the lack of absolute differences in T-cell subsets, the combination of CD8 effector 1, CD16-positive monocytes, and CD56-positive NK profiles may help to identify responders to DKRd treatment. Expansion of CD16-positive monocytes associated with sustained MRD negativity was observed when patients achieved a complete response to induction.
Disclosure: Dr. Boyle reported no conflicts of interest. For full disclosures of the other study authors, visit ash.confex.com.
2022 ASH Annual Meeting and Exposition
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