Multiple myeloma future or investigational therapies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2] Shyam Patel [3]
Overview
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.
Future or Investigational Therapies
Chimeric antigen receptor T (CAR-T) cell therapy
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]
Other investigational therapies
- 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]
References
- ↑ 1.0 1.1 Makita S, Yoshimura K, Tobinai K (2017). "Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma". Cancer Sci. 108 (6): 1109–1118. doi:10.1111/cas.13239. PMC 5480083. PMID 28301076.
- ↑ Bu DX, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG; et al. (2018). "Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma". Oncotarget. 9 (40): 25764–25780. doi:10.18632/oncotarget.25359. PMC 5995247. PMID 29899820.
- ↑ Rasche, L.; Strifler, S.; Duell, J.; Rosenwald, A.; Buck, A.; Maeder, U.; Einsele, H.; Knop, S. (2014). "The lymphoma-like polychemotherapy regimen Dexa-BEAM in advanced and extramedullary multiple myeloma". Ann Hematol. doi:10.1007/s00277-014-2023-2. PMID 24526137. Unknown parameter
|month=ignored (help) - ↑ Eda, H.; Santo, L.; Cirstea, DD.; Yee, A.; Scullen, TA.; Nemani, N.; Mishima, Y.; Waterman, PR.; Arastu-Kapur, S. (2014). "A novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant anti-myeloma activity". Leukemia. doi:10.1038/leu.2014.69. PMID 24518207. Unknown parameter
|month=ignored (help)