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== Investigational therapies == | == Investigational therapies == | ||
* Recent advances in the understanding of the [[pathogenesis]] of | * Recent advances in the understanding of the [[pathogenesis]] of mantle cell lymphoma have led to the development of targeted therapies which have shown potential promise as effective [[therapeutic]] approaches in the future.. | ||
* In addition to the ongoing assessment of new [[Monoclonal antibody therapy|monoclonal antibody-based therapies]], the continued development of targeted [[molecular]] [[Signaling molecule|signaling]] inhibitors based on the underlying [[biology]] of | * In addition to the ongoing assessment of new [[Monoclonal antibody therapy|monoclonal antibody-based therapies]], the continued development of targeted [[molecular]] [[Signaling molecule|signaling]] inhibitors based on the underlying [[biology]] of MCL is an approach that will potentially yield fruitful results in this [[disease]]. | ||
* Some of the current therapies under [[clinical]] investigation are as follows: | * Some of the current therapies under [[clinical]] investigation are as follows: | ||
**[[BCL-2]] inhibitor [[venetoclax]] (ABT-199) and the phosphatydilinosytol 3-kinase δ ([[PI3K]] δ) inhibitor [[idelalisib]] were tested in a [[Phase I trial|phase I]] study and have shown promising results.<ref>{{Cite journal | **[[BCL-2]] inhibitor [[venetoclax]] (ABT-199) and the phosphatydilinosytol 3-kinase δ ([[PI3K]] δ) inhibitor [[idelalisib]] were tested in a [[Phase I trial|phase I]] study and have shown promising results.<ref>{{Cite journal | ||
| Line 28: | Line 28: | ||
| pmid = 30190341 | | pmid = 30190341 | ||
}}</ref> | }}</ref> | ||
** [[Chimeric protein|Chimeric]] [[antigen]] [[receptor]] [[T cell|T-cell]] (CAR-T) [[therapy]] is being used in a [[phase II]] study of CAR-T therapy in relapsed | ** [[Chimeric protein|Chimeric]] [[antigen]] [[receptor]] [[T cell|T-cell]] (CAR-T) [[therapy]] is being used in a [[phase II]] study of CAR-T therapy in relapsed MCL.<ref>{{Cite journal | ||
| author = [[James N. Kochenderfer]], [[Mark E. Dudley]], [[Sadik H. Kassim]], [[Robert P. T. Somerville]], [[Robert O. Carpenter]], [[Maryalice Stetler-Stevenson]], [[James C. Yang]], [[Giao Q. Phan]], [[Marybeth S. Hughes]], [[Richard M. Sherry]], [[Mark Raffeld]], [[Steven Feldman]], [[Lily Lu]], [[Yong F. Li]], [[Lien T. Ngo]], [[Andre Goy]], [[Tatyana Feldman]], [[David E. Spaner]], [[Michael L. Wang]], [[Clara C. Chen]], [[Sarah M. Kranick]], [[Avindra Nath]], [[Debbie-Ann N. Nathan]], [[Kathleen E. Morton]], [[Mary Ann Toomey]] & [[Steven A. Rosenberg]] | | author = [[James N. Kochenderfer]], [[Mark E. Dudley]], [[Sadik H. Kassim]], [[Robert P. T. Somerville]], [[Robert O. Carpenter]], [[Maryalice Stetler-Stevenson]], [[James C. Yang]], [[Giao Q. Phan]], [[Marybeth S. Hughes]], [[Richard M. Sherry]], [[Mark Raffeld]], [[Steven Feldman]], [[Lily Lu]], [[Yong F. Li]], [[Lien T. Ngo]], [[Andre Goy]], [[Tatyana Feldman]], [[David E. Spaner]], [[Michael L. Wang]], [[Clara C. Chen]], [[Sarah M. Kranick]], [[Avindra Nath]], [[Debbie-Ann N. Nathan]], [[Kathleen E. Morton]], [[Mary Ann Toomey]] & [[Steven A. Rosenberg]] | ||
| title = Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor | | title = Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor | ||
| Line 40: | Line 40: | ||
| pmid = 25154820 | | pmid = 25154820 | ||
}}</ref> | }}</ref> | ||
**Due to the [[male]] to [[female]] predominance of approximately 4:1 in | **Due to the [[male]] to [[female]] predominance of approximately 4:1 in MCL, investigators are investigating [[androgen receptor]] (AR) blockers like [[enzalutamide]] as means of decreasing MCL cell proliferation.<ref>{{Cite journal | ||
| author = [[Elahe A. Mostaghel]], [[Paul S. Martin]], [[Stephen Mongovin]], [[Shani Frayo]], [[Ailin Zhang]], [[Kerstin L. Edlefsen]], [[Oliver W. Press]] & [[Ajay K. Gopal]] | | author = [[Elahe A. Mostaghel]], [[Paul S. Martin]], [[Stephen Mongovin]], [[Shani Frayo]], [[Ailin Zhang]], [[Kerstin L. Edlefsen]], [[Oliver W. Press]] & [[Ajay K. Gopal]] | ||
| title = Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications | | title = Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications | ||
| Line 51: | Line 51: | ||
| pmid = 28115200 | | pmid = 28115200 | ||
}}</ref> | }}</ref> | ||
**A few next-generation [[Proteasome inhibitor|proteasome inhibitors]] ([[carfilzomib]], oprozomib, [[ixazomib]]) are undergoing clinical testing in | **A few next-generation [[Proteasome inhibitor|proteasome inhibitors]] ([[carfilzomib]], oprozomib, [[ixazomib]]) are undergoing clinical testing in MCL and have shown an acceptable safety profile in [[bortezomib]]-resistant MCL patients.<ref>{{Cite journal | ||
| author = [[Hun J. Lee]], [[Maria Badillo]], [[Jorge Romaguera]] & [[Michael Wang]] | | author = [[Hun J. Lee]], [[Maria Badillo]], [[Jorge Romaguera]] & [[Michael Wang]] | ||
| title = A phase II study of carfilzomib in the treatment of relapsed/refractory mantle cell lymphoma | | title = A phase II study of carfilzomib in the treatment of relapsed/refractory mantle cell lymphoma | ||
Latest revision as of 20:26, 7 January 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2]
Investigational therapies
- Recent advances in the understanding of the pathogenesis of mantle cell lymphoma have led to the development of targeted therapies which have shown potential promise as effective therapeutic approaches in the future..
- In addition to the ongoing assessment of new monoclonal antibody-based therapies, the continued development of targeted molecular signaling inhibitors based on the underlying biology of MCL is an approach that will potentially yield fruitful results in this disease.
- Some of the current therapies under clinical investigation are as follows:
- BCL-2 inhibitor venetoclax (ABT-199) and the phosphatydilinosytol 3-kinase δ (PI3K δ) inhibitor idelalisib were tested in a phase I study and have shown promising results.[1][2]
- Chimeric antigen receptor T-cell (CAR-T) therapy is being used in a phase II study of CAR-T therapy in relapsed MCL.[3]
- Due to the male to female predominance of approximately 4:1 in MCL, investigators are investigating androgen receptor (AR) blockers like enzalutamide as means of decreasing MCL cell proliferation.[4]
- A few next-generation proteasome inhibitors (carfilzomib, oprozomib, ixazomib) are undergoing clinical testing in MCL and have shown an acceptable safety profile in bortezomib-resistant MCL patients.[5]
References
- ↑ Brad S. Kahl, Stephen E. Spurgeon, Richard R. Furman, Ian W. Flinn, Steven E. Coutre, Jennifer R. Brown, Don M. Benson, John C. Byrd, Sissy Peterman, Yoonjin Cho, Albert Yu, Wayne R. Godfrey & Nina D. Wagner-Johnston (2014). "A phase 1 study of the PI3Kdelta inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL)". Blood. 123 (22): 3398–3405. doi:10.1182/blood-2013-11-537555. PMID 24615778. Unknown parameter
|month=ignored (help) - ↑ Toby A. Eyre, Harriet S. Walter, Sunil Iyengar, George Follows, Matthew Cross, Christopher P. Fox, Andrew Hodson, Josh Coats, Santosh Narat, Nick Morley, Martin J. S. Dyer & Graham P. Collins (2018). "Efficacy of venetoclax monotherapy in patients with relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy". Haematologica. doi:10.3324/haematol.2018.198812. PMID 30190341. Unknown parameter
|month=ignored (help) - ↑ James N. Kochenderfer, Mark E. Dudley, Sadik H. Kassim, Robert P. T. Somerville, Robert O. Carpenter, Maryalice Stetler-Stevenson, James C. Yang, Giao Q. Phan, Marybeth S. Hughes, Richard M. Sherry, Mark Raffeld, Steven Feldman, Lily Lu, Yong F. Li, Lien T. Ngo, Andre Goy, Tatyana Feldman, David E. Spaner, Michael L. Wang, Clara C. Chen, Sarah M. Kranick, Avindra Nath, Debbie-Ann N. Nathan, Kathleen E. Morton, Mary Ann Toomey & Steven A. Rosenberg (2015). "Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 33 (6): 540–549. doi:10.1200/JCO.2014.56.2025. PMID 25154820. Unknown parameter
|month=ignored (help) - ↑ Elahe A. Mostaghel, Paul S. Martin, Stephen Mongovin, Shani Frayo, Ailin Zhang, Kerstin L. Edlefsen, Oliver W. Press & Ajay K. Gopal (2017). "Androgen receptor expression in mantle cell lymphoma: Potential novel therapeutic implications". Experimental hematology. 49: 34–38. doi:10.1016/j.exphem.2017.01.001. PMID 28115200. Unknown parameter
|month=ignored (help) - ↑ Hun J. Lee, Maria Badillo, Jorge Romaguera & Michael Wang (2018). "A phase II study of carfilzomib in the treatment of relapsed/refractory mantle cell lymphoma". British journal of haematology. doi:10.1111/bjh.15107. PMID 29527676. Unknown parameter
|month=ignored (help)