With support from the International Myeloma Society, this project aims to revolutionize the diagnosis and treatment of Multiple Myeloma (MM) in Sub-Saharan Africa. MM patients in the region often face late diagnoses and limited access to genomic tools that guide personalized care. Current treatment strategies are based on data from non-African populations, overlooking the unique … Continued

We hypothesize that tumor-immune microenvironment and macroenvironment alterations shape MM progression and treatment resistance. The problem is that the current understanding of immune resilience vs loss of function in MM is limited and, because of it, there are no immune biomarkers ready for primetime use in laboratory diagnostics. The consequence of this problem is that … Continued

Smoldering multiple myeloma (SMM) represents a common precursor stage to active multiple myeloma (MM), yet accurately predicting early progression in SMM remains a challenge. Traditional risk models, such as the Mayo 20-2-20 system rely on disease burden parameters and have been validated to predict the risk of progression to active myeloma but fail to capture … Continued

Resistance to therapy remains a significant challenge in multiple myeloma, often driven by the substantial genetic heterogeneity inherent to this disease. This now includes resistance to state-of-the-art immunotherapies targeting BCMA. To address this critical challenge, we propose to develop a novel, multi-agent therapeutic strategy designed to overcome resistance and improve outcomes for patients with relapsed … Continued

Light chain (AL) amyloidosis is a fatal plasma cell disorder related to multiple myeloma, characterized by clonal plasma cells that produce excess misfolded immunoglobulin light chains—either the κ or λ subtype—which aggregate into amyloid fibrils, causing organ damage and ultimately leading to death. Current therapies targeting plasma cells can suppress further fibril production but do … Continued

Immunotherapy with monoclonal antibodies and their use in combination with proteasome inhibitors and immunomodulatory agents have revolutionized treatment of multiple myeloma (MM). Chimeric antigen receptor (CAR) T cells and bispecific T cell engagers (TCE) further improved the outcome of a substantial number of patients. Nevertheless, for relapsed/refractory myeloma (RRMM) patients there is still a high … Continued

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized the treatment of refractory B-cell malignancies. Nevertheless, in multiple myeloma (MM), despite a high rate of initial response, these responses tend not to be durable, important contributory factors including intrinsic cancer cell resistance and immune suppression within the tumor microenvironment (TME). Emerging evidence highlights the role … Continued

The overarching objective of this proposal is to decipher the intricate molecular pathways, underlying myeloma-induced bone disease (MBD), a critical aspect of multiple myeloma pathogenesis. Employing state-of-the-art imaging, genomic and proteomic analyses, the proposal seeks to unravel the complex interplay between myeloma cells and the bone microenvironment. The objective of the proposal is to establish … Continued

Chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective therapeutic approach in multiple myeloma (MM), where two B cell maturation antigen (BCMA)-targeting CAR-T products, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), are currently approved in the relapsed/refractory MM (RRMM) setting. The outstanding outcomes manifested in overall response rates (ORR) above 70% in heavily … Continued