Chimeric antigen receptor T (CAR-T) cell therapy is actively under study for the treatment of relapsed and refractory multiple myeloma. This form of cell-based therapy employs one’s own T lymphocytes, which are engineered to be tumor-specific. The antigen of interest for multiple myeloma CAR-T therapy is B cell maturation antigen (BCMA). Other investigational therapies include lymphoma-like polychemotherapy regimen and Bruton’s tyrosine kinase inhibitor CC-292.

Chimeric antigen receptor T (CAR-T) cell therapy has recently been approved by the Food and Drug Administration for the treatment of acute lymphoblastic leukemia and diffuse large B cell lymphoma in the second- or third-line settings. CAR-T therapy is currently being explored for the treatment of multiple myeloma. This form of therapy involves the engineering of a patient’s own T lymphocytes to create genetically engineered cells that have anti-tumor immune responses. The process of CAR-T construction involves first performing leukopheresis to collect peripheral blood mononuclear cells, which contain the T cell population. The T cells are stimulated to proliferated via treatment with interleukin-2 (IL-2) or anti-CD3 agonist antibody.^[1] A lentivirus or retrovirus is transfected into the T cells, and this lentivirus contains the DNA sequence that encodes for the CAR gene. The final CAR-T cell product is usually composed of 3 components: a single-chain variable fragment, a transmembrane domain, and an intracellular signal transduction domain. This structure allows for antigen recognition that parallels B lymphocyte activity and effector function that parallels T lymphocyte activity, hence the name “chimeric.”^[1] CAR-T cells are a combination of T cells and antibodies and are thus sometimes known as “T-bodies.” In multiple myeloma, the specific tumor antigen against which CAR-T cells are engineered is B cell maturation antigen, or BCMA. Studies on the safety and efficacy are still pending, but the pre-clinical validation has already been completed.^[2]

• Lymphoma-like polychemotherapy: The regimen “Dexa-BEAM” (including dexamethasone, carmustine, cytarabine, etoposide and melphalan) in treating advanced and extramedullary multiple myeloma has been studied. It showed improved survival when used as a bridge to stem cell transplantation.^[3]

• CC-292: The novel Bruton’s tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib has been studied for the treatment of multiple myeloma.^[4]

Template:WikiDoc Sources