Frontline Combination CAR-T Cell Therapy for Multiple Myeloma or Plasmacytoma

Multiple myeloma (MM) is the second most common malignant hematological cancer in the world, which begins with the malignant proliferation of plasma cells in bone marrow. It has been a difficult disease to treat, and most patients will eventually relapse, especially for those with high-risk genotypes. At present, the therapeutic drugs for MM include glucocorticoids, cytotoxic drugs, immunosuppressants, protease inhibitors, monoclonal antibodies and cell therapies. Among those, immunotherapy has been proven to be a revolutionary treatment with great potential of curing this disease. The frequently targeted MM antigens include CD38, CD138, CD19 and BCMA, and recently, GPRC5D.

BCMA, the B cell maturation antigen, also known as CD269 or TNFRSF17, is a member of tumor necrosis factor receptor superfamily, which is highly expressed on the surface of plasma cells and partially expressed on plasma cell-like dendritic cells. It has been an ideal target for MM immunotherapy.

GPRC5D, the G-protein-coupled receptor C57 subtype D and a seven-transmembrane protein, is highly expressed on the surface of plasma cells but not in other healthy cells, and thus it has become a potential target for the treatment of MM. The expression of GPRC5D is unrelated to BCMA, so the combination therapy targeting these antigens may bring a complementary and synergistic therapeutic outcome in patients.

This trial is aimed to test the safety and efficacy of combining these different CAR-T cells targeting BCMA and GPRC5D, and in combination with well-established therapeutics as a frontline treatment for the high-risk MM or plasmacytoma patients. Another goal of this study is to investigate the persistence and function of these CAR-T cells in the body.