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In vitro comparison of cytotoxic effects of bortezomib resistant U266 myeloma cell line (U266/VELR) on combination of ibrutinib with carfilzomib and lenalidomid drugs

Year 2019, Volume: 41 Issue: 4, 698 - 702, 31.12.2019
https://doi.org/10.7197/cmj.vi.664928

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.

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.
Year 2019, Volume: 41 Issue: 4, 698 - 702, 31.12.2019
https://doi.org/10.7197/cmj.vi.664928

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

Hatice Terzi 0000-0003-3471-1305

Merve Ergül 0000-0003-4661-8087

Publication Date December 31, 2019
Acceptance Date December 31, 2019
Published in Issue Year 2019Volume: 41 Issue: 4

Cite

AMA Terzi H, Ergül M. In vitro comparison of cytotoxic effects of bortezomib resistant U266 myeloma cell line (U266/VELR) on combination of ibrutinib with carfilzomib and lenalidomid drugs. CMJ. December 2019;41(4):698-702. doi:10.7197/cmj.vi.664928