330
Views
1
CrossRef citations to date
0
Altmetric
Reviews

Pharmacologic maintenance strategies following allogeneic hematopoietic cell transplantation for acute myeloid leukemia

, &
Pages 516-527 | Received 04 May 2016, Accepted 19 Jun 2016, Published online: 11 Aug 2016

References

  • Grunwald MR, Levis MJ. FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol. 2013;97:683–694.
  • Illmer T, Ehninger G. FLT3 kinase inhibitors in the management of acute myeloid leukemia. Clin Lymphoma Myeloma. 2007;8:S24–S34.
  • Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136–1152.
  • Brandts CH, Sargin B, Rode M, et al. Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Cancer Res. 2005;65:9643–9650.
  • Kelly LM, Liu Q, Kutok JL, et al. FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood. 2002;99:310–318.
  • 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;99:4326–4335.
  • Burnett AK, Goldstone A, Hills RK, et al. Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission. J Clin Oncol. 2013;31:1293–1301.
  • 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;98:1752–1759.
  • Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100:59–66.
  • Gale RE, Hills R, Kottaridis PD, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood. 2005;106:3658–3665.
  • Yanada M, Matsuo K, Suzuki T, et al. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia. 2005;19:1345–1349.
  • Meshinchi S, Alonzo TA, Stirewalt DL, et al. Clinical implications of FLT3 mutations in pediatric AML. Blood. 2006;108:3654–3661.
  • Frohling S, Schlenk RF, Breitruck J, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002;100:4372–4380.
  • Bornhauser M, Illmer T, Schaich M, et al. Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML. Blood. 2007;109:2264–2265; author reply 2265.
  • Lin PH, Lin CC, Yang HI, et al. Prognostic impact of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with internal tandem duplication of FLT3. Leuk Res. 2013;37:287–292.
  • 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;30:735–741.
  • DeZern AE, Sung A, Kim S, et al. Role of allogeneic transplantation for FLT3/ITD acute myeloid leukemia: outcomes from 133 consecutive newly diagnosed patients from a single institution. Biol Blood Marrow Transplant. 2011;17:1404–1409.
  • Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909–1918.
  • Laboure G, Dulucq S, Labopin M, et al. Potent graft-versus-leukemia effect after reduced-intensity allogeneic SCT for intermediate-risk AML with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD. Biol Blood Marrow Transplant. 2012;18:1845–1850.
  • Ma Y, Wu Y, Shen Z, et al. Is allogeneic transplantation really the best treatment for FLT3/ITD-positive acute myeloid leukemia? A systematic review. Clin Transplant. 2015;29:149–160.
  • Deol A, Sengsayadeth S, Ahn KW, et al. Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis. Cancer. 2016. [Epub ahead of print]. doi: 10.1002/cncr.30140.
  • Konig H, Levis M. Targeting FLT3 to treat leukemia. Expert Opin Ther Targets. 2015;19:37–54.
  • Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109.
  • Kruger WH, Hirt C, Kiefer T, et al. Molecular remission of FLT3-ITD(+) positive AML relapse after allo-SCT by acute GVHD in addition to sorafenib. Bone Marrow Transplant. 2012;47:137–138.
  • Winkler J, Rech D, Kallert S, et al. Sorafenib induces sustained molecular remission in FLT3-ITD positive AML with relapse after second allogeneic stem cell transplantation without exacerbation of acute GVHD: a case report. Leuk Res. 2010;34:e270–e272.
  • Sora F, Chiusolo P, Metafuni E, et al. Sorafenib for refractory FMS-like tyrosine kinase receptor-3 (FLT3/ITD+) acute myeloid leukemia after allogenic stem cell transplantation. Leuk Res. 2011;35:422–423.
  • De Freitas T, Marktel S, Piemontese S, et al. High rate of hematological responses to sorafenib in FLT3-ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation. Eur J Haematol. 2016;96:629–636.
  • Sammons SL, Pratz KW, Smith BD, et al. Sorafenib is tolerable and improves clinical outcomes in patients with FLT3-ITD acute myeloid leukemia prior to stem cell transplant and after relapse post-transplant. Am J Hematol. 2014;89:936–938.
  • 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;26:2353–2359.
  • Chen YB, Li S, Lane AA, et al. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for FMS-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20:2042–2048.
  • Brunner AM, Li S, Fathi AT, et al. Hematopoietic cell transplantation with or without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukemia in CR1. Blood. 2015;126:Abstract 864.
  • 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;1:433–443.
  • Stone R, Mandrekar S, Sanford BL, et al. The multi-kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)/cytarabine (C) induction (ind), high-dose consolidation (consol), and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (9AML) patients (pts) age 18–60 with FLT3 mutation (muts): an International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY) [Alliance]. Available from: https://ash.confex.com/ash/2015/webprogram/Paper80269.html.
  • Schlenk R, Döhner K, Salih H, et al. Midostaurin in combination with intensive induction and as single agent maintenance therapy after consolidation therapy with allogeneic hematopoietic stem cell transplantation or high-dose cytarabine (NCT01477606). Blood. 2015;126:Abstract 322.
  • Levis M. Quizartinib for the treatment of FLT3/ITD acute myeloid leukemia. Future Oncol. 2014;10:1571–1579.
  • 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;31:3681–3687.
  • Cortes JE, Perl AE, Dombret H, et al. Final results of a phase 2 open-label, monotherapy efficacy and safety study of quizartinib (AC220) in patients ≥60 years of age with FLT3 ITD positive or negative relapsed/refractory acute myeloid leukemia. Blood. 2012;120:Abstract 48.
  • Levis MJ, Perl AE, Dombret H, et al. 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. Blood. 2012;120:Abstract 673.
  • Schiller GJ, Tallman MS, Goldberg SL, et al. Final results of a randomized phase 2 study showing the clinical benefit of quizartinib (AC220) in patients with FLT3-ITD positive relapsed or refractory acute myeloid leukemia. J Clin Oncol. 2014;32(suppl 5):Abstract 7100.
  • Sandmaeier BM, Khaled SK, Oran B, et al. Results of a phase 1 study of quizartinib (AC220) as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic cell transplantation. Blood. 2014;124:Abstract 428.
  • Oran B. Is there a role for therapy after transplant? Best Pract Res Clin Haematol. 2015;28:124–132.
  • Stein EM, Tallman MS. Tallman MS. Emerging therapeutic drugs for AML. Blood. 2016;127:71–78.
  • 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;485:260–263.
  • 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.
  • Collins R, Kantarjian HM, Levis MJ, et al. Clinical activity of crenolanib in patients with D835 mutant FLT3-positive relapsed/refractory acute myeloid leukemia (AML). J Clin Oncol. 2014;32(5s):Abstract 7027.
  • Altman JK, Perl AE, Cortes JE, et al. Antileukemic activity and tolerability of ASP2215 80 mg and greater in FLT3 mutation-positive subjects with relapsed or refractory acute myeloid leukemia: results from a phase 1/2, open-label, dose-escalation/dose-response study. Blood. 2015;126:Abstract 321.
  • Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670–2677.
  • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28:562–569.
  • Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–299.
  • Sockel K, Wermke M, Radke J, et al. Minimal residual disease-directed preemptive treatment with azacitidine in patients with NPM1-mutant acute myeloid leukemia and molecular relapse. Haematologica. 2011;96:1568–1570.
  • Czibere A, Bruns I, Kroger N, et al. 5-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis. Bone Marrow Transplant. 2010;45:872–876.
  • Goodyear OC, Dennis M, Jilani NY, et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood. 2012;119:3361–3369.
  • Choi J, Ritchey J, Prior JL, et al. In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood. 2010;116:129–139.
  • Jabbour E, Giralt S, Kantarjian H, et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer. 2009;115:1899–1905.
  • de Lima M, Giralt S, Thall PF, et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 2010;116:5420–5431.
  • Craddock C, Jilani N, Siddique S, et al. Tolerability and clinical activity of post-transplantation azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial. Biol Blood Marrow Transplant. 2016;22:385–390.
  • Vij R, Hars V, Blum W, et al. CALGB 100801 (Alliance): A Phase II Multi-Center NCI Cooperative Group Study of the addition of azacitidine (AZA) to reduced-intensity conditioning (RIC) allogeneic transplantation for high risk myelodysplasia (MDS) and older patients with acute myeloid leukemia (AML): results of a “test dose” strategy to target busulfan exposure. Blood. 2012;124:Abstract 543.
  • de Lima M. New approaches to transplantation in acute myelogenous leukemia. Hematology Am Soc Hematol Educ Program. 2015;2015:596–604.
  • Pusic I, Choi J, Fiala MA, et al. Maintenance therapy with decitabine after allogeneic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2015;21:1761–1769.
  • Stahl M, Gore SD, Vey N, et al. Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Expert Opin Investig Drugs. 2016;25:307–317.
  • Tan P, Wei A, Mithraprabhu S, et al. Dual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood Cancer J. 2014;4:e170.
  • Govindaraj C, Tan P, Walker P, et al. Reducing TNF receptor 2+ regulatory T cells via the combined action of azacitidine and the HDAC inhibitor, panobinostat for clinical benefit in acute myeloid leukemia patients. Clin Cancer Res. 2014;20:724–735.
  • Issa JP, Garcia-Manero G, Huang X, et al. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015;121:556–561.
  • Shen L, Pili R. Class I histone deacetylase inhibition is a novel mechanism to target regulatory T cells in immunotherapy. Oncoimmunology. 2012;1:948–950.
  • Bug G, Burchert A, Wagner E, et al. Phase I/II study of the deacetylase inhibitor panobinostat as maintenance therapy after an allogeneic stem cell transplantation in patients with high-risk MDS or AML: the Panobest-Trial. Blood. 2015;126:Abstract 4344.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.