Transcriptomic Signatures of Early Mortality in Multiple Myeloma Patients Treated with Immunomodulatory RVD Therapy 4758

Abstract Description Multiple myeloma (MM) remains a clinically challenging hematological malignancy with high relapse rates and mortality despite advancements in treatment. This study aimed to identify transcriptomic signatures associated with early mortality in newly diagnosed MM patients undergoing the standard lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD) therapy. We analyzed RNA-seq data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass study (NCT01454297) and applied Weighted Gene Co-expression Network Analysis (WGCNA) as well as Kaplan–Meier survival, gene ontology enrichment, differential gene expression, and ROC analysis, which revealed six hub genes (NTRK1, CBX2, NUP133, DNA2, NUF2, and KIF7) within co-expression networks that are strongly associated with early mortality. Given that lenalidomide, a key component of the RVD regimen, exerts its therapeutic effect partly through immunomodulatory mechanisms, these findings suggest that the identified genes may influence patient outcomes by modulating the interplay between MM cells and the immune system. Further investigation of these genes and their roles in the context of lenalidomide’s immunomodulatory effects could lead to improved risk stratification and personalized treatment strategies for MM patients. Funding Sources NIH/NCI award #U54CA118638, NIH/NIGMS award #R25GM058268, and the Chan Zuckerberg Initiative Accelerate Precision Health Program award #CZIF2002-007045. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)