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Investigational FMS-like tyrosine kinase 3 inhibitors in treatment of acute myeloid leukemia

, , , & , MD

Bibliography

  • Daver N, Liu Dumlao T, Ravandi F, et al. Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute Myeloid Leukemia receiving standard chemotherapy. Clin Lymphoma Myeloma Leuk 2013;13:435-40
  • Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol 2007;25:1908-15
  • Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with Acute Myeloid Leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001;98:1312-20
  • Frohling S, Schlenk RF, Kayser S, et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 2006;108:3280-8
  • Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 2011;29:475-86
  • Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001;98:1752-9
  • Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002;99:4326-35
  • Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program 2013;2013:220-6
  • Fathi AT. Emergence of crenolanib for FLT3-mutant AML. Blood 2013;122:3547-8
  • Takahashi K, Kantarjian H, Pemmaraju N, et al. Salvage therapy using FLT3 inhibitors may improve long-term outcome of relapsed or refractory AML in patients with FLT3-ITD. Br J Haematol 2013;161:659-66
  • Kayser S, Levis MJ. FLT3 tyrosine kinase inhibitors in acute myeloid leukemia: clinical implications and limitations. Leuk Lymphoma 2014;55(2):243-55
  • Brunet S, Labopin M, Esteve J, et al. Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hematopoietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis. J Clin Oncol 2012;30:735-41
  • Sharma M, Ravandi F, Bayraktar UD, et al. Treatment of FLT3-ITD-positive acute myeloid leukemia relapsing after allogeneic stem cell transplantation with sorafenib. Biol Blood Marrow Transplant 2011;17:1874-7
  • Hu B, Vikas P, Mohty M, Savani BN. Allogeneic stem cell transplantation and targeted therapy for FLT3/ITD+ acute myeloid leukemia: an update. Expert Rev Hematol 2014;7(2):301-15
  • Pratz KW, Levis MJ. Bench to bedside targeting of FLT3 in acute leukemia. Curr Drug Targets 2010;11:781-9
  • Pemmaraju N, Kantarjian H, Ravandi F, Cortes J. FLT3 inhibitors in the treatment of acute myeloid leukemia: the start of an era? Cancer 2011;117(15):3293-304
  • Sawyers CL. Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia. Cancer Cell 2002;1:413-15
  • Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002;346:645-52
  • Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-7
  • Brown P, Small D. FLT3 inhibitors: a paradigm for the development of targeted therapeutics for paediatric cancer. Eur J Cancer 2004;40:707-21. discussion 22; 4
  • Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 2000;19:624-31
  • Tse KF, Mukherjee G, Small D. Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation. Leukemia 2000;14:1766-76
  • Levis M, Tse KF, Smith BD, et al. A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood 2001;98:885-7
  • Kelly LM, Yu JC, Boulton CL, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell 2002;1:421-32
  • Weisberg E, Boulton C, Kelly LM, et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 2002;1:433-43
  • Small D. FLT3 mutations: biology and treatment. Hematology Am Soc Hematol Educ Program 2006;178-84
  • Knapper S. FLT3 inhibition in acute myeloid leukaemia. Br J Haematol 2007;138:687-99
  • Zimmerman EI, Turner DC, Buaboonnam J, et al. Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia. Blood 2013;122:3607-15
  • Smith CC, Lasater EA, Lin KC, et al. Crenolanib is a selective type I pan-FLT3 inhibitor. Proc Natl Acad Sci USA 2014. [ Epub ahead of print]
  • Galanis A, Ma H, Rajkhowa T, et al. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood 2014;123:94-100
  • Ahmad T, Eisen T. Kinase inhibition with BAY 43-9006 in renal cell carcinoma. Clin Cancer Res 2004;10:6388S-92S
  • Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90
  • Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356:125-34
  • Haraldsdottir S, Shah MH. An update on clinical trials of targeted therapies in thyroid cancer. Curr Opin Oncol 2014;26:36-44
  • Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005;23:965-72
  • Zhang W, Konopleva M, Shi YX, et al. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst 2008;100:184-98
  • Zhang W, Konopleva M, Ruvolo VR, et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia 2008;22:808-18
  • Rollig C, Brandts C, Shaid S, et al. Survey and analysis of the efficacy and prescription pattern of sorafenib in patients with acute myeloid leukemia. Leuk Lymphoma 2012;53:1062-7
  • Crump M, Hedley D, Kamel-Reid S, et al. A randomized phase I clinical and biologic study of two schedules of sorafenib in patients with myelodysplastic syndrome or acute myeloid leukemia: a NCIC (National Cancer Institute of Canada) Clinical Trials Group Study. Leuk Lymphoma 2010;51:252-60
  • Borthakur G, Kantarjian H, Ravandi F, et al. Phase I study of sorafenib in patients with refractory or relapsed acute leukemias. Haematologica 2011;96:62-8
  • Inaba H, Rubnitz JE, Coustan-Smith E, et al. Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia. J Clin Oncol 2011;29:3293-300
  • Sayar H, Cripe L, Cangany M, et al. Cyclic administration of combination of Sorafenib and Vorinostat in poor-risk AML: a pharmacodynamically-oriented extended phase I trial. ASH Annual Meeting Abstracts 2010;116:3272
  • Serve H, Wagner R, Sauerland C, et al. Sorafenib in combination with standard induction and consolidation therapy in elderly AML patients: results from a randomized, placebo-controlled phase II trial. ASH Annual Meeting Abstracts 2010;116:333
  • Ravandi F, Cortes JE, Jones D, et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol 2010;28:1856-62
  • Levis M, Brown P, Smith BD, et al. Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood 2006;108:3477-83
  • Pratz KW, Cho E, Levis MJ, et al. A pharmacodynamic study of sorafenib in patients with relapsed and refractory acute leukemias. Leukemia 2010;24:1437-44
  • Sato T, Yang X, Knapper S, et al. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood 2011;117:3286-93
  • Cortes JE, Kantarjian H, Foran JM, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol 2013;31:3681-7
  • Ravandi F, Alattar ML, Grunwald MR, et al. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood 2013;121:4655-62
  • Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011;117:3294-301
  • Zarrinkar PP, Gunawardane RN, Cramer MD, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood 2009;114:2984-92
  • Smith CC, Chin J, Wang Q, et al. Validation of FLT3-ITD as a therapeutic target in human Acute Myeloid Leukemia. ASH Annual Meeting Abstracts 2011;118:937
  • Sexauer A, Perl A, Yang X, et al. Terminal myeloid differentiation in vivo is induced by FLT3 inhibition in FLT3/ITD AML. Blood 2012;120:4205-14
  • Cortes JE, Perl AE, Smith CC, et al. A phase II open-label, Ac220 monotherapy efficacy study in patients with refractory/relapsed FLT3-Itd positive Acute Myeloid Leukemia: updated interim results. ASH Annual Meeting Abstracts 2011;118:2576
  • Levis MJ PA, Dombret H, Dohner H. Final results of a phase 2 open-label, monotherapy efficacy and safety study of Quizartinib (AC220) in patients with FLT3-ITD positive or negative relapsed/refractory Acute Myeloid Leukemia after second-line chemotherapy or hematopoietic stem cell transplantation. ASH Annual Meeting Abstracts 2012 2012
  • Burnett AK, Russell N, Knapper S. AC220 (Quizartinib) can be safely combined with conventional chemotherapy in older patients with newly diagnosed Acute Myeloid Leukaemia: experience from the AML18 pilot trial. ASH Annual Meeting Abstracts 2013
  • Altman JK, Foran JM, Pratz KW, et al. Results of a phase 1 study of Quizartinib (AC220, ASP2689) in combination with induction and consolidation chemotherapy in younger patients with newly diagnosed Acute Myeloid Leukemia. ASH Annual Meeting Abstracts 2013
  • Millward MJ, House C, Bowtell D, et al. The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer 2006;95:829-34
  • Barry EV, Clark JJ, Cools J, et al. Uniform sensitivity of FLT3 activation loop mutants to the tyrosine kinase inhibitor midostaurin. Blood 2007;110:4476-9
  • Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol 2010;28:4339-45
  • Williams CB, Kambhampati S, Fiskus W, et al. Preclinical and phase I results of Decitabine in combination with Midostaurin (PKC412) for newly diagnosed elderly or relapsed/refractory adult patients with Acute Myeloid Leukemia. Pharmacotherapy 2013;33:1341-52
  • Nazha A, Kantarjian HM, Borthakur G, et al. A Phase I/II trial of combination of Midostaurin (PKC412) and 5-Azacytidine (5-AZA) for the treatment of patients with refractory or relapsed (R/R) Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). ASH Annual Meeting Abstracts 2012;120:3587
  • Stone RM, Fischer T, Paquette R, et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia 2012;26:2061-8
  • Lancet JE. New agents: great expectations not realized. Best Pract Res Clin Haematol 2013;26:269-74
  • Heinrich MC, Griffith D, McKinley A, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res 2012;18:4375-84
  • Smith CC, Lasater EA, Zhu X, et al. Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD. Blood 2013;121:3165-71
  • Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 2013;369:1783-96
  • Gozgit JM, Wong MJ, Wardwell S, et al. Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther 2011;10:1028-35
  • Zirm E, Spies-Weisshart B, Heidel F, et al. Ponatinib may overcome resistance of FLT3-ITD harbouring additional point mutations, notably the previously refractory F691I mutation. Br J Haematol 2012;157:483-92
  • Shah NP, Talpaz M, Deininger MW, et al. Ponatinib in patients with refractory acute myeloid leukaemia: findings from a phase 1 study. Br J Haematol 2013;162:548-52
  • Safaian NN, Czibere A, Bruns I, et al. Sorafenib (Nexavar) induces molecular remission and regression of extramedullary disease in a patient with FLT3-ITD+ acute myeloid leukemia. Leuk Res 2009;33:348-50
  • Metzelder SK, Schroeder T, Finck A, et al. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia 2012;26:2353-9
  • Lin WH, Yeh TK, Jiaang WT, et al. Evaluation of the antitumor effects of BPR1J-340, a potent and selective FLT3 inhibitor, alone or in combination with an HDAC inhibitor, Vorinostat, in AML cancer. PLoS One 2014;9:e83160
  • Ma H, Nguyen B, Li L, et al. TTT-3002 is a novel FLT3 tyrosine kinase inhibitor with activity against FLT3-associated leukemias in vitro and in vivo. Blood 2014. [ Epub ahead of print]
  • Reikvam H, Nepstad I, Tamburini J. Predicting effects of kinase inhibitor in therapy for myeloid malignancies - the challenges in capturing disease heterogeneity. Expert Opin Investig Drugs 2013;22:1365-70
  • Man CH, Fung TK, Ho C, et al. Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood 2012;119:5133-43
  • Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012;485:260-3
  • Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9
  • Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 2009;113:6215-24
  • Zeng Z, Samudio IJ, Munsell M, et al. Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated chemoresistance in chronic and acute leukemias. Mol Cancer Ther 2006;5:3113-21
  • Andreeff M ZZ, Kelly MA, et al. Targeting microenvironment-mediated resistance in leukemias: phase I trial of mobilization and elimination of FLT3-ITD+ acute myelogenous leukemia (AML) stem/progenitor cells by plerixafor/g-CSF/sorafenib. J Clin Oncol 2012;30(Suppl):Abstract TPS6635
  • Konopleva MY, Jordan CT. Leukemia stem cells and microenvironment: biology and therapeutic targeting. J Clin Oncol 2011;29:591-9
  • Konopleva M, Tabe Y, Zeng Z, Andreeff M. Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches. Drug Resist Updat 2009;12:103-13
  • Jin L, Tabe Y, Lu H, et al. Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment. Cancer Lett 2013;329:45-58
  • Kurosu T, Nagao T, Wu N, et al. Inhibition of the PI3K/Akt/GSK3 pathway downstream of BCR/ABL, Jak2-V617F, or FLT3-ITD downregulates DNA damage-induced Chk1 activation as well as G2/M arrest and prominently enhances induction of apoptosis. PLoS ONE 2013;8:e79478
  • Baker SD, Zimmerman EI, Wang YD, et al. Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia. Clin Cancer Res 2013;19:5758-68
  • Nelson EA, Walker SR, Xiang M, et al. The STAT5 inhibitor Pimozide displays efficacy in models of Acute Myelogenous Leukemia driven by FLT3 mutations. Genes Cancer 2012;3:503-11
  • Puissant A, Fenouille N, Alexe G, et al. SYK is a critical regulator of FLT3 in Acute Myeloid Leukemia. Cancer Cell 2014;25:226-42
  • Derenzini E, Younes A. Targeting the JAK-STAT pathway in lymphoma: a focus on pacritinib. Expert Opin Investig Drugs 2013;22:775-85
  • Weisberg E, Liu Q, Nelson E, et al. Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors and JAK inhibitors. Leukemia 2012;26:2233-44
  • Reikvam H, Nepstad I, Bruserud O, Hatfield KJ. Pharmacological targeting of the PI3K/mTOR pathway alters the release of angioregulatory mediators both from primary human acute myeloid leukemia cells and their neighboring stromal cells. Oncotarget 2013;4:830-43
  • Reikvam H, Tamburini J, Skrede S, et al. Antileukaemic effect of PI3K-mTOR inhibitors in acute myeloid leukaemia-gene expression profiles reveal CDC25B expression as determinate of pharmacological effect. Br J Haematol 2014;164:200-11
  • Chen W, Drakos E, Grammatikakis I, et al. mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3-mutated acute myeloid leukemia cells. Mol Cancer 2010;9:292
  • Keegan K, Li C, Li Z, et al. Preclinical evaluation of AMG 925, a FLT3/CDK4 dual kinase inhibitor for treating acute myeloid leukemia. Mol Cancer Ther 2014. [ Epub ahead of print]
  • Hart S, Goh KC, Novotny-Diermayr V, et al. Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. Blood Cancer J 2011;1:e44

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