Display options
Cite
Gallogly MM, Lazarus HM. Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016;7:73-83doi: 10.2147/JBM.S100283.
Gallogly, M. M., & Lazarus, H. M. (2016). Midostaurin: an emerging treatment for acute myeloid leukemia patients. Journal of blood medicine, 773-83. https://doi.org/10.2147/JBM.S100283
Gallogly, Molly Megan, and Lazarus, Hillard M. "Midostaurin: an emerging treatment for acute myeloid leukemia patients." Journal of blood medicine vol. 7 (2016): 73-83. doi: https://doi.org/10.2147/JBM.S100283
Gallogly MM, Lazarus HM. Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016 Apr 19;7:73-83. doi: 10.2147/JBM.S100283. eCollection 2016. PMID: 27186148; PMCID: PMC4848023.
Copy Download .nbib Format: NLM
Share it on

J Blood Med. 2016 Apr 19;7:73-83. doi: 10.2147/JBM.S100283. eCollection 2016.

Midostaurin: an emerging treatment for acute myeloid leukemia patients.

Journal of blood medicine

Molly Megan Gallogly, Hillard M Lazarus

Affiliations

  1. Department of Medicine, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.

PMID: 27186148 PMCID: PMC4848023 DOI: 10.2147/JBM.S100283

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin's ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are investigating midostaurin's role in pretransplant induction and posttransplant consolidation therapy.

Keywords: FLT3; acute leukemia; clinical trial; midostaurin; myelodysplastic syndrome

References

  1. Cancer Chemother Pharmacol. 2013 Dec;72 (6):1223-34 - PubMed
  2. Future Oncol. 2015 Sep;11(18):2499-501 - PubMed
  3. Pharmacol Ther. 1999 May-Jun;82(2-3):293-301 - PubMed
  4. Leukemia. 2013 Feb;27(2):260-8 - PubMed
  5. Clin Pharmacokinet. 2008;47(12 ):807-16 - PubMed
  6. N Engl J Med. 2015 Sep 17;373(12):1136-52 - PubMed
  7. Cancer Cell. 2002 Jun;1(5):433-43 - PubMed
  8. J Clin Pharmacol. 2008 Jun;48(6):763-75 - PubMed
  9. Blood. 2009 Sep 17;114(12):2386-92 - PubMed
  10. Blood. 2013 Nov 21;122(22):3607-15 - PubMed
  11. Pharmacotherapy. 2013 Dec;33(12 ):1341-52 - PubMed
  12. J Clin Oncol. 2013 Sep 1;31(25):3110-8 - PubMed
  13. Leukemia. 2014 Dec;28(12):2276-82 - PubMed
  14. Blood. 2005 Jan 1;105(1):54-60 - PubMed
  15. Am J Hematol. 2015 Apr;90(4):276-81 - PubMed
  16. Nagoya J Med Sci. 2015 Feb;77(1-2):7-17 - PubMed
  17. J Clin Oncol. 2013 Oct 10;31(29):3681-7 - PubMed
  18. Blood. 2002 Dec 15;100(13):4372-80 - PubMed
  19. Cancer Res. 2001 Oct 1;61(19):7233-9 - PubMed
  20. Blood. 2010 Feb 18;115(7):1425-32 - PubMed
  21. Clin Lymphoma Myeloma Leuk. 2015 Jul;15(7):428-432.e2 - PubMed
  22. Blood. 2011 Jul 28;118(4):1069-76 - PubMed
  23. Blood. 2006 Jan 1;107(1):293-300 - PubMed
  24. Leukemia. 2012 Sep;26(9):2061-8 - PubMed
  25. J Natl Compr Canc Netw. 2015 May;13(5):508-14 - PubMed
  26. Curr Hematol Malig Rep. 2014 Jun;9(2):174-85 - PubMed
  27. Anticancer Drug Des. 2000 Feb;15(1):17-28 - PubMed
  28. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29 - PubMed
  29. N Engl J Med. 2012 Mar 22;366(12):1079-89 - PubMed
  30. Semin Hematol. 2015 Jul;52(3):193-9 - PubMed
  31. Blood. 2009 Oct 1;114(14 ):2984-92 - PubMed
  32. Curr Opin Oncol. 2009 Nov;21(6):594-600 - PubMed
  33. Ann Hematol. 2010 Jul;89(7):653-62 - PubMed
  34. N Engl J Med. 2008 May 1;358(18):1909-18 - PubMed
  35. J Clin Oncol. 2001 Mar 1;19(5):1485-92 - PubMed
  36. J Clin Oncol. 2010 Oct 1;28(28):4339-45 - PubMed

Publication Types