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ASH 2021 | scRNA-seq of the immune microenvironment reveals immunotherapy response biomarkers in high-risk SMM

Clinical and genomic biomarkers can aid the identification of patients with smoldering multiple myeloma (SMM) who are at high risk of progression to overt multiple myeloma. However, it is not yet clear whether additional characterization of the tumor immune microenvironment could aid prognostication. Irene Ghobrial, MD, Dana-Farber Cancer Institute, Boston, MA, comments on a study that used single-cell RNA-sequencing (scRNA-seq) on CD138-immune cells from patients with high-risk SMM to investigate potential immune biomarkers. Samples were taken at baseline, at the start of cycle 9, and at the end of treatment from patients enrolled in a Phase II trial of elotuzumab, lenalidomide, and dexamethasone. It was shown that a higher abundance of mature B-cells, Th17 cells, and GZMK cells was associated with significantly longer progression-free survival (PFS) in SMM patients. These differences reflect how normal-like a patient’s immune composition is at baseline. Those with a not normal-like immune composition, potentially reflecting the immune system’s reactive capacity, had significantly improved PFS. Additionally, those with immune normalization at the end of treatment has significantly longer PFS. These findings suggest baseline immune reactivity and post-therapy immune normalization could aid optimal patient selection and response assessment. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.