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]
Overview
The lymphoma-like polychemotherapy regimen, carfilzomib, and Bruton's tyrosine kinase inhibitor CC-292 are investigational therapies for the treatment of multiple myeloma.
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]
- Lymphoma-like polychemotherapy regimen "Dexa-BEAM" (including dexamethasone, carmustine, cytarabine, etoposide and melphalan) in treating advanced and extramedullary multiple myeloma has been studied by Rasche L etal. It showed improved survival, when used as a bridge to stem cell transplantation.[3]
- Carfilzomib is a new proteasome inhibitor that selectively and irreversibly binds to its target, resulting in sustained inhibition. It thus has a better response as compared to bortezomib along with a favorable safety profile. Clinical trials have been approved and under process to study the effects of the drug. The prospect of its combination with several other agents such as immunomodulators, alkylating agents, glucocorticoids, histone deacetylase inhibitors and kinesin spindle protein inhibitors also holds promise.[4]
- novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib and its rols as anti-multiple myeloma combiantion therpay.[5]
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) - ↑ Moreau, P. (2014). "The emerging role of carfilzomib combination therapy in the management of multiple myeloma". Expert Rev Hematol. doi:10.1586/17474086.2014.873699. PMID 24521249. 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)