Despite major advances in multiple myeloma therapy, patients with high-risk disease — particularly those with t(4;14) multiple myeloma and extramedullary disease — remain at increased risk of relapse, including after modern immune therapies such as CAR T cells and T-cell engagers. This project will investigate how genomic features of myeloma cells shape the spatial organization of the immune microenvironment in bone marrow and extramedullary lesions.
Using high-resolution Xenium-based spatial RNA/protein profiling integrated with whole-genome sequencing, the study will define how tumor cells and immune cells interact within “tumor fortress” regions that may exclude T cells and promote immune escape. The project will focus especially on t(4;14) myeloma and paired bone marrow/extramedullary disease biopsies. Findings from this work are expected to refine biological definitions of high-risk disease, identify immune and genomic biomarkers of resistance, and inform development of clinically feasible assays and therapeutic strategies to improve outcomes for patients with high-risk multiple myeloma.
Madhav V. Dhodapkar, MBBS
Professor
Fred Hutch Cancer Center
Evan Newell, PhD
Professor
Fred Hutch Cancer Center
Fred Hutch will contribute expertise in high-resolution spatial profiling and computational spatial biology, including Xenium spatial transcriptomic/protein panel development, spatial data generation and optimization, and advanced analytic approaches to characterize tumor–immune architecture. Fred Hutch will work closely with MSK on harmonization, integration, interpretation, and publication of the spatial and genomic datasets.
Francesco Maura, MD
Dept of Medicine
Myeloma Service
Memorial Sloak Kettering Cancer Center
Ross Firestone, MD, PhD
Assistant Attending
Memorial Sloak Kettering Cancer Center
MSK will lead the clinical and genomic components of the project, including identification and characterization of patient cohorts enriched for t(4;14) multiple myeloma, integration of whole-genome sequencing data, analysis of tumor genetic features, and correlation of genomic/spatial findings with clinical outcomes. MSK will also contribute paired bone marrow and extramedullary disease biopsy analyses where available.