Our preliminary data demonstrate that CST6N137D prevents downmodulation of the CAR on the surface of CAR-T cells, maintains persistence of CAR-T cells in the body, and enhances therapeutic killing of MM cells by CAR-T cells. In this application, we will (1) determine whether CST6N137D suppresses lysosomal degradation, thereby preventing CAR downmodulation; and (2) determine the … Continued
The project aims to uncover how the bone marrow microenvironment allows tumor cells to survive treatment and cause relapse in multiple myeloma. Dormancy refers to a state in which residual tumor cells persist without net growth. The dormant cells evade both cytotoxic drugs and immune surveillance, later reactivating to drive relapse. A critical barrier to … Continued
Multiple myeloma remains an incurable malignancy, with most patients ultimately relapsing due to therapy-resistant disease. While the genetic landscape of multiple myeloma is highly heterogeneous, malignant plasma cells often converge on shared transcriptional dependencies that sustain tumor survival. Among these, the transcription factor TCF3 has emerged as a highly selective and previously unexplored vulnerability in … Continued
Anti-BCMA CAR-T cell therapies achieve deep responses in relapsed/refractory multiple myeloma, yet most patients eventually relapse, largely due to limited long-term persistence and progressive dysfunction of CAR-T cells under chronic tumor antigen exposure. SHIELD-MM addresses this critical limitation by developing a next-generation version of ARI0002h — an academic anti-BCMA CAR-T product authorized by the Spanish … Continued
Our project investigates how malignant plasma cells cope with the stress associated with high antibody production. While current therapies already exploit the fragility of these cells by interfering with protein degradation systems, the mechanisms that sustain this intense protein production remain poorly understood. Our research focuses on a newly emerging layer of regulation that controls … Continued
We have recently evaluated IL-18-secreting dual-CAR T cells targeting BCMA and BAFF-R in a syngeneic mouse model of multiple myeloma as a comprehensive approach to simultaneously overcome multiple CAR T cell failure mechanisms. Engineered IL-18 secretion by BCMA and BAFF-R-targeting CAR T cells enabled elimination of antigen-low myeloma, stimulated macrophage killing of myeloma cells, activated … Continued
This project aims to determine whether DNA damage response–associated clonal hematopoiesis (DDR-CH) predicts therapy-related myeloid neoplasms in multiple myeloma patients receiving autologous stem cell transplantation and lenalidomide maintenance. Specific aims include characterizing CH prevalence at pre- and post-ASCT timepoints using ultra-deep error-corrected targeted sequencing, testing whether DDR-CH but not age-related CH confers tMN risk, and … Continued
The curative potential of BCMA CART cells is still suboptimal, with antigen escape and an unfavorable tumor microenvironment contributing to disease relapse. In this project, we aim to overcome these challenges by enhancing established BCMA CART cells with additional multi-antigen specificity by the generation of Conventional and Adapter Dual CART cells (ConvAD CART cells). Our … Continued
Over the past two decades, therapeutic advances have continuously improved the management of multiple myeloma, opening up a genuine prospect of cure. However, certain treatment-related side effects remain frequent and may compromise therapeutic efficacy. This is particularly the case for venous thromboembolism, whose risk persists despite the use of pharmacological prophylaxis and validated risk-assessment scores. … Continued
This project investigates APOBEC3B (A3B) as a biomarker and therapeutic vulnerability in high-risk multiple myeloma with TP53 aberrations. Through the integration of patient-derived datasets, genetically engineered model systems, and primary patient samples, the study aims to define biologically aggressive A3B-high disease states and uncover targetable stress-response dependencies that may inform more precise treatment strategies for … Continued
Why Become a Member
The International Myeloma Society is a professional, scientific, and medical society established to bring together clinical and experimental scientists involved in the study of myeloma. The purpose of this society is to promote research, education, clinical studies (including diagnosis and treatment), workshops, conferences, and symposia on all aspects of multiple myeloma worldwide.
The IMS is a membership organization comprised of basic research scientists, and clinical investigators in the field along with physicians and other healthcare practitioners.
