Systematic multiomic profiling of tumor and immune cells for non invasive detection of early myeloma
Bruno Paiva
PhDUniversidad de Navarra
Project Term: October 1, 2021 - September 30, 2024
Multiple myeloma remains largely incurable and there is consensus that the pathway to cure cancer involves treating patients earlier. Thus, there is an unmet need to develop methods for early detection of pre-malignant disease and to help tailoring treatment for patients with smoldering myeloma. We aim to develop new methods for minimally invasive characterization of patients with smoldering myeloma in order to treat disease causation instead of symptomatology and increase curability rates.
Although we made great strides in the management of multiple myeloma, our best chances to eradicate this malignancy may lie in preventing its progression in the first place. Thus, we aim to treat disease causation instead of symptomatology by integrating next-generation immunophenotypic and genomic profiling, and develop new methods based on minimally invasive characterization of circulating tumor and immune cells to identify patients with smoldering myeloma at risk of developing active disease. We will determine how the immunophenotypic and genomic signatures of tumor and immune cells from 300 patients with smoldering myeloma evolve every six months in peripheral blood, from stable to progressive disease. We will evaluate the number and genomic profile of circulating tumor cells over time as critical biomarkers to predict risk of transformation in smoldering myeloma, and compare immune profiles between patients with benign vs pre-malignant smoldering myeloma to define immune signatures related to disease stability vs progression. Data will be integrated with current stratification models based on serological, imaging and invasive bone marrow assessments. Altogether, the simultaneous availability of effective, well-tolerated (immuno)therapies together with next-generation phenotypic and sequencing technologies, creates momentum for new, minimally-invasive methods to detect patients with smoldering myeloma at risk of transformation, offer precision medicine to prevent disease progression, and increase curability rates. This project is tasked to deliver such methods.