Projects & Grants
| Analysis of Circulating Tumor Plasma Cells in Multiple Myeloma Patients Treated with Immunotherapies Targeting BCMA and GPRC5D | |
|---|---|
| Project Id | |
| Main solver | Mgr. Eva Radová |
| Period | 1/2025 - 12/2025 |
| Provider | Specifický VŠ výzkum |
| State | solved |
| Anotation | Multiple myeloma (MM) is a disease characterized by clonal proliferation of plasma cells within the bone marrow. In most patients, these malignant cells disseminate into peripheral blood, where they are called circulating tumor plasma cells (CTCs). Higher levels of CTCs are associated with a more aggressive disease course, poor prognosis, and an increased risk of progression, thus representing a significant prognostic factor. Peripheral blood sampling is less invasive and safer compared to a traditional bone marrow biopsy, while still providing comparably valuable information about MM biology, mechanisms of resistance, or prediction of treatment response. In recent years, significant progress has been made in the treatment of MM mainly due to the identification of new therapeutic targets such as BCMA and GPRC5D. These antigens are highly expressed on the surface of malignant plasma cells, and immunotherapies targeting BCMA and GPRC5D are extremely effective in patients with relapsed/refractory MM (RRMM). Approved therapies targeting these antigens include bispecific antibodies like teclistamab, elranatamab, and talquetamab, as well as CAR-T cell therapies such as cilta-cel and ide-cel. Due to mutational or epigenetic changes in the genes encoding these antigens, this treatment may be initially ineffective (mutation or reduced expression before starting treatment). However, during initially effective treatment, selection pressure can lead to mutations or dysregulation of the targeted genes, causing more resistant clones to expand and ultimately resulting in progression or relapse. This research will focus on the evaluation of peripheral blood CTCs in patients before and after treatment with modern immunotherapies targeting BCMA and GPRC5D antigens. The objective is to obtain a sufficient amount of CTCs in RRMM to monitor mutations in the genes encoding these antigens and to elucidate the mechanisms underlying treatment resistance. |
