High-dimensional Clonal Heterogeneity and Immune Landscape in Multiple Myeloma

The results of a study presented at the 17th International Myeloma Workshop might provide the rational for predicting multiple myeloma (MM) patient status for targeted and immune therapy.

Researchers performed a large-scale mass cytometry (CyTOF) analysis of bone marrow (BM) samples from 188 MM patients matched with 10 age-matched healthy donors (HD). Subsequently, they designed a pipeline for deep characterization of plasma cells (PC) within the immune ecosystem of the myeloma microenvironment and analyzed the BM of 104 MM patients comprised of 16 with monoclonal gammopathy of undetermined significance (MGUS), 25 patients with smoldering MM (SMM), 43 patients with newly diagnosed multiple myeloma (NDMM) and relapsed or relapsed/refractory MM patients.

After profiling for PC based on molecular and transcriptional factors to ensure B cell development, the results showed that switched memory B cells and plasmablast clusters were upregulated in MGUS patients compared to HD patients. Researchers observed similar findings in SMM and NDMM juxtaposed to HD, with the highest number of PC clusters in NDMM patients. The downregulation of cell distribution in B cell progenies, immature and transitional B cells, and un-switched memory B cell clusters was observed in NDMM patients. Moreover, the study found a significant upregulation in the expression of CD47 in all PC clusters in the MM group.

Furthermore, PC clusters differed in the markers CD184, Notch-1, Oct3/4, KLF-4, Sox-2, Nestin and Nanog, which, as the researchers wrote, support “the idea of sub-clonal variations insight of MM tumor.”

“Interaction of PC with myeloma immuno-ecosystem showed that immune clusters differ with significant abundance in subsets of T helper cells, non-canonical monocytes, and subsets of myeloid lineage, whereas decrease of cell distribution in immature T and B cells, promonocytes and cytotoxic T cell subsets was observed in MM cohort compared to HD,” the researchers continued.

They added that the “upregulation of KIR expression was more pronounced in adaptive immune clusters, whereas PD-1 immune checkpoint was mostly increased in innate immune clusters.”

Jakubikova J, et al. High-dimensional Clonal Heterogeneity and Immune Landscape in Multiple Myeloma. Presented at the 17th International Myeloma Workshop; September 12-15, 2019; Boston, MA.