Multiple myeloma future or investigational therapies: Difference between revisions
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{{Multiple myeloma}} | {{Multiple myeloma}} | ||
{{CMG}} {{AE}}{{VB}} | {{CMG}} {{AE}}{{VB}} {{shyam}} | ||
==Overview== | ==Overview== | ||
The lymphoma-like polychemotherapy regimen | 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== | ==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.<ref name="pmid28301076">{{cite journal| author=Makita S, Yoshimura K, Tobinai K| title=Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma. | journal=Cancer Sci | year= 2017 | volume= 108 | issue= 6 | pages= 1109-1118 | pmid=28301076 | doi=10.1111/cas.13239 | pmc=5480083 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28301076 }} </ref> 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."<ref name="pmid28301076">{{cite journal| author=Makita S, Yoshimura K, Tobinai K| title=Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma. | journal=Cancer Sci | year= 2017 | volume= 108 | issue= 6 | pages= 1109-1118 | pmid=28301076 | doi=10.1111/cas.13239 | pmc=5480083 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28301076 }} </ref> 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.<ref name="pmid29899820">{{cite journal| author=Bu DX, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG et al.| title=Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. | journal=Oncotarget | year= 2018 | volume= 9 | issue= 40 | pages= 25764-25780 | pmid=29899820 | doi=10.18632/oncotarget.25359 | pmc=5995247 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29899820 }} </ref> | |||
*[[ | ===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]].<ref name="Rasche-2014">{{Cite journal | last1 = Rasche | first1 = L. | last2 = Strifler | first2 = S. | last3 = Duell | first3 = J. | last4 = Rosenwald | first4 = A. | last5 = Buck | first5 = A. | last6 = Maeder | first6 = U. | last7 = Einsele | first7 = H. | last8 = Knop | first8 = S. | title = The lymphoma-like polychemotherapy regimen Dexa-BEAM in advanced and extramedullary multiple myeloma. | journal = Ann Hematol | volume = | issue = | pages = | month = Feb | year = 2014 | doi = 10.1007/s00277-014-2023-2 | PMID = 24526137 }}</ref> | |||
* | *'''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.<ref name="Eda-2014">{{Cite journal | last1 = Eda | first1 = H. | last2 = Santo | first2 = L. | last3 = Cirstea | first3 = DD. | last4 = Yee | first4 = A. | last5 = Scullen | first5 = TA. | last6 = Nemani | first6 = N. | last7 = Mishima | first7 = Y. | last8 = Waterman | first8 = PR. | last9 = Arastu-Kapur | first9 = S. | title = 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. | journal = Leukemia | volume = | issue = | pages = | month = Feb | year = 2014 | doi = 10.1038/leu.2014.69 | PMID = 24518207 }}</ref> | ||
== References == | == References == | ||
Latest revision as of 00:49, 20 August 2018
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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)