Immune Profiling Reveals Distinct Features of Multiple Myeloma Subtypes Defined By Multi-Omics Network Analysis

• Published in: Blood 2024-11, Vol.144, p.4658-4658
• Main Authors: Vieira, Junia, Park, Alison S, Gonzalez-Kozlova, Edgar, Melnekoff, David, Bhalla, Sherry, Acharya, Chaitanya, Hamilton, Mark, Mulligan, George, Network, Immune Atlas, Cho, Hearn Jay, Ding, Li, Gnjatic, Sacha, Vlachos, Ioannis S, Bhasin, Manoj, Jagannath, Sundar, Parekh, Samir, Lagana, Alessandro
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-208677

Introduction: Multiple myeloma (MM) has a highly heterogeneous genomic landscape, challenging patient stratification and clinical management. By combining bulk tumor profiling with single-cell data of the tumor microenvironment (TME), we aimed to create a comprehensive multi-omics network model to dissect inter-tumor heterogeneity, which enabled us to characterize the immune cell landscape and correlate it with patient subgroups identified through multi-omics analysis of bulk tumor data, revealing significant features within each subgroup. Methods: We analyzed 185 samples collected at diagnosis from newly-diagnosed MM (NDMM) patients in MMRF CoMMpass, included in both our previous MM-PSN model (Bhalla et al, 2021) and the MMRF Immune Atlas (Pilcher et al, 2023). The CD138- fraction underwent 10X 3' single cell RNA seq (scRNA-seq), yielding 776,859 cells. Our dataset included 107,884 myeloid cells, 407,895 NK/T cells, 162,630 B/ erythroid cells, and 85,147 plasma cells. The analysis was performed using the R packages Seurat, CellphoneDB, pySCENIC, MOVICS and MOGONET. Results: We stratified 185 patients in the Immune Atlas cohort according to our multi-omics patient similarity network MM-PSN into the following groups: (i) hyperdiploidy (HD) and t(8;14) translocation of MYC (tMYC) (group 1, n = 105); (ii) translocations t(4;14) of MMSET (tMMSET) and t(14;16) of MAF (tMAF) (group 2, n = 46); and (iii) translocation t(11;14) of CCND1 (tCCND1) (group 3, n = 33). The overall cohort had a median progression-free survival (PFS) of 1082 days. The subgroups had the following median PFS: HD, 1094 days; tMMSET/tMAF, 634 days; and tCCND1, 1236 days. Group 1 had higher frequencies of hematopoietic stem cells (HSCs), plasmacytoid dendritic cells (pDCs) and B naïve cells (p