Research Article
In vitro comparison of cytotoxic effects of bortezomib resistant U266 myeloma cell line (U266/VELR) on combination of ibrutinib with carfilzomib and lenalidomid drugs
Abstract
Objective: Multiple myeloma is still one of the incurable hematologic cancers. It
is a common problem of all hematologists to look for new combinations in this malignancy,
that treatment steps are rapidly depleted.
Method: The
cytotoxic activities of carfilzomib, lenalidomide and their combination with
ibrutinib were evaluated using the XTT colorimetric assay on U266B1/BR cells.
Cells were seeded into 96-well plates at a density of 1×104 cells
per well, incubated with various concentrations of ibrutinib, carfilzomib,
lenalidomide and their combinations for 24h and 48h.
Results: In our
study, we found that adding ibrutinib to carfilzomib and lenalidomide
combination in Bortezomib refractory myeloma cell line did not increase
cytotoxicity.
Conclusions: Further clinical and experimental studies are needed
to demonstrate the efficacy of ibrutinib in which many B-cell malignancy has
been demonstrated.
Keywords
References
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- 2. Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenstrom's macroglobulinemia. N Engl J Med. 2015;372:1430-40.
- 3. Kim ES, Dhillon S. Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Drugs. 2015;75:769-76.
- 4. Gourzones C, Bret C, Moreaux J. Treatment May Be Harmful: Mechanisms/Prediction/Prevention of Drug-Induced DNA Damage and Repair in Multiple Myeloma. Front Genet. 2019;10:861.
- 5. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122-1128.
- 6. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-152.
- 7. Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24(1):22-32.
- 8. Niesvizky R, Martin TG, 3rd, Bensinger WI et al. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Clin. Cancer Res. 2013;19(8):2248-2256.
- 9. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A Phase I/II study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012;120(9):1801-9.
- 10. Davids MS, Brown JR. Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase. Future Oncol. 2014;10:957-67.
- 11. Berglof A, Turunen JJ, Gissberg O, Bestas B, Blomberg KE, Smith CI. A gamma globulinemia: causative mutations and their implications for novel therapies. Exp Rev Clin Immunol. 2013;9:1205-21.
- 12. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015;94:193-205. 13. Vargas L, Hamasy A, Nore BF, Smith CI. Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Scand J Immunol. 2013;78:130-9.
Year 2019,
, 698 - 702, 31.12.2019
Abstract
References
- 1. Lindvall JM, Blomberg KE, Valiaho J, et al. Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Immunol Rev. 2005;203:200-15.
- 2. Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenstrom's macroglobulinemia. N Engl J Med. 2015;372:1430-40.
- 3. Kim ES, Dhillon S. Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Drugs. 2015;75:769-76.
- 4. Gourzones C, Bret C, Moreaux J. Treatment May Be Harmful: Mechanisms/Prediction/Prevention of Drug-Induced DNA Damage and Repair in Multiple Myeloma. Front Genet. 2019;10:861.
- 5. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122-1128.
- 6. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-152.
- 7. Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24(1):22-32.
- 8. Niesvizky R, Martin TG, 3rd, Bensinger WI et al. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Clin. Cancer Res. 2013;19(8):2248-2256.
- 9. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A Phase I/II study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012;120(9):1801-9.
- 10. Davids MS, Brown JR. Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase. Future Oncol. 2014;10:957-67.
- 11. Berglof A, Turunen JJ, Gissberg O, Bestas B, Blomberg KE, Smith CI. A gamma globulinemia: causative mutations and their implications for novel therapies. Exp Rev Clin Immunol. 2013;9:1205-21.
- 12. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015;94:193-205. 13. Vargas L, Hamasy A, Nore BF, Smith CI. Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Scand J Immunol. 2013;78:130-9.
There are 12 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Medical Science Research Articles |
| Authors | |
| Publication Date | December 31, 2019 |
| Acceptance Date | December 31, 2019 |
| Published in Issue | Year 2019 |