Spatial heterogeneity assessment in myeloma

Maximilian Merz, MD, Roswell Park Comprehensive Center Institute, Buffalo, NY, explains the results of an investigation of spatial heterogeneity and immunogenomics in newly diagnosed and relapsed/refractory multiple myeloma. 18 patients underwent sampling of iliac crest bone marrow as well as an osteolytic lesion, on which whole-exome sequencing and single-cell RNAseq was performed. The results showed that median plasma cell (PC) infiltration was higher in osteolytic lesions than random OM, at 50.0% vs 12.5%, respectively. Branching evolution was seen in osteolytic lesion derived plasma cells of 4 patients. Patients showed spatially divergent clones, with differences in expression of genes for bone marrow homing, malignant transformation, and apoptosis. When immune cells were analyzed, site-specific clone expansion was seen, as well as a decrease in TCR diversity in patients with relapsed/refractory myeloma. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.