Multiple Myeloma is a Hematologic Malignancy Characterized by the Accumulation of Malignant Plasma Cells in the Bone Marrow. Despite Advances in Treatment, Many Patients Experience Disease Relapse. Bispecific Antibodies Offer an Innovative Therapeutic Approach, But Approximately 30%-40% of Patients

This prospective, non-interventional study aims to characterize the molecular and cellular mechanisms underlying the response and resistance of multiple myeloma (MM) patients to bispecific antibodies (BisAb) and CAR-T therapies. Conducted at the Tel Aviv Sourasky Medical Center, the study will enroll up to 200 MM patients aged 18 and older, who are candidates for BisAb, CAR-T, or other MM treatments. Bone marrow (4-6 mL) and peripheral blood (15-20 mL) samples will be collected before treatment and at predefined intervals post-treatment, including at disease relapse/progression. The study will analyze plasma cells and the tumor microenvironment (TME) using techniques such as flow cytometry (FACS), single-cell RNA sequencing, genomic DNA sequencing, and ELISA to assess soluble BCMA levels. Key objectives include identifying genetic and protein signatures predictive of treatment response, evaluating specific drug binding, and analyzing interactions between plasma cells and immune cells (e.g., T cells). Samples will be processed and stored at the study site, with data coded to ensure patient confidentiality. Results will inform personalized treatment strategies for MM patients. The study duration includes 5 years for sample collection, 1 year for data analysis, and up to 20 years for sample storage.