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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Review

Precision therapy for acute myeloid leukemia

Authors: Xue Yang, Jianxiang Wang

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous disease. Despite advances in understanding the pathogenesis of AML, the standard therapy remained nearly unchanged over the past three decades. With the poor survival for older patients and high relapse rate, multiple studies are ongoing to address this important issue. Novel therapies for AML, including the refinements of conventional cytotoxic chemotherapies and genetic and epigenetic targeted drugs, as well as immunotherapies, have been developed in recent years. Here, we present a mechanism-based review of some promising new drugs with clinical efficacy, focus on targeted drugs that are most potential to pave the road to success, and put forward the major challenges in promoting the precision therapy for AML.
Literature
1.
Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.PubMedCrossRef
2.
3.
4.
5.
Marcucci G, Haferlach T, Döhner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol. 2011;29:475–86.PubMedCrossRef
6.
Zeijlemaker W, Gratama J-W, Schuurhuis G. Tumor heterogeneity makes AML a “moving target” for detection of residual disease. Cytometry B Clin Cytom. 2014;86:3–14.PubMedCrossRef
7.
McCulloch EA. Stem cells in normal and leukemic hemopoiesis (Henry Stratton Lecture). Blood. 1983;62:1–13.PubMed
8.
9.
Ravandi F, Burnett AK, Agura ED, Kantarjian HM. Progress in the treatment of acute myeloid leukemia. Cancer. 2007;110:1900–10.PubMedCrossRef
10.
Kantarjian H, Ravandi F, O'Brien S, Cortes J, Faderl S, Garcia-Manero G, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116:4422–9.PubMedPubMedCentralCrossRef
11.
Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361:1249–59.PubMedPubMedCentralCrossRef
12.
Lee J-H, Joo Y-D, Kim H, Bae SH, Kim MK, Zang DY, et al. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011;118:3832–41.PubMedCrossRef
13.
Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016;127:1551–8.PubMedPubMedCentralCrossRef
14.
Willemze R, Suciu S, Meloni G, Labar B, Marie J-P, Halkes CJ, et al. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2013;32:219–28.PubMedCrossRef
15.
Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012;30:2441–8.PubMedCrossRef
16.
Kantarjian H, Gandhi V, Cortes J, Verstovsek S, Du M, Garcia-Manero G, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102:2379–86.PubMedCrossRef
17.
Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, et al. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013;122:1384–94.PubMedCrossRef
18.
Löwenberg B, Pabst T, Maertens J, van Norden Y, Biemond BJ, Schouten HC, et al. Therapeutic value of clofarabine in younger and middle aged (18–65 years) adults with newly diagnosed AML. Blood. 2017;129:1636–45.PubMedCrossRef
19.
Mayer LD, Harasym TO, Tardi PG, Harasym NL, Shew CR, Johnstone SA, et al. Ratiometric dosing of anticancer drug combinations: controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice. Mol Cancer Ther. 2006;5:1854–63.PubMedCrossRef
20.
21.
Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, et al. Phase 2 trial of CPX-351, a fixed 5: 1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014;123:3239–46.PubMedPubMedCentralCrossRef
22.
Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, et al. Phase II, multicenter, randomized trial of CPX-351 (cytarabine: daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2015;121:234–42.PubMedCrossRef
23.
Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235–48.PubMedCrossRef
24.
Stuart RK, Cripe LD, Maris MB, Cooper MA, Stone RM, Dakhil SR, et al. REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia. Br J Haematol. 2015;168:796–805.PubMedCrossRef
25.
Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, et al. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015;16:1025–36.PubMedPubMedCentralCrossRef
26.
Döhner H, Lübbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, et al. Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy. Blood. 2014;124:1426–33.PubMedPubMedCentralCrossRef
27.
Ferrara F. New agents for acute myeloid leukemia: is it time for targeted therapies? Expert Opin Investig Drugs. 2012;21:179–89.PubMedCrossRef
28.
Daver N, Konopleva M. Sorafenib and novel multikinase inhibitors in AML. Lancet Oncol. 2015;16:1582–3.PubMedCrossRef
29.
Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, 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.PubMedCrossRef
30.
Marcucci G, Maharry K, Whitman SP, Vukosavljevic T, Paschka P, Langer C, et al. High expression levels of the ETS-related gene, ERG, predict adverse outcome and improve molecular risk-based classification of cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B Study. J Clin Oncol. 2007;25:3337–43.PubMedCrossRef
31.
Borthakur G, Kantarjian H, Patel KP, Ravandi F, Qiao W, Faderl S, et al. Impact of numerical variation in FMS-like tyrosine kinase receptor 3 internal tandem duplications on clinical outcome in normal karyotype acute myelogenous leukemia. Cancer. 2012;118:5819–22.PubMedPubMedCentralCrossRef
32.
Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood. 2010;115:1425–32.PubMedPubMedCentralCrossRef
33.
Sudhindra A, Smith CC. FLT3 inhibitors in AML: are we there yet? Curr Hematol Malig Rep. 2014;9:174–85.PubMedCrossRef
34.
Smith CC, Wang Q, Chin C-S, Salerno S, Damon LE, Levis MJ, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012;485:260–3.PubMedPubMedCentralCrossRef
35.
Borthakur G, Kantarjian H, Ravandi F, Zhang W, Konopleva M, Wright JJ, et al. Phase 1 study of sorafenib in patients with refractory or relapsed acute leukemias. Haematologica. 2011;96:62–8.PubMedCrossRef
36.
Lee SH, Paietta E, Racevskis J, Wiernik PH. Complete resolution of leukemia cutis with sorafenib in an acute myeloid leukemia patient with FLT3-ITD mutation. Am J Hematol. 2009;84:701–2.PubMedCrossRef
37.
Metzelder SK, Wollmer E, Neubauer A, Burchert A. Sorafenib in relapsed and refractory FLT3-ITD positive acute myeloid leukemia: a novel treatment option. Dtsch Med Wochenschr. 2010;135:1852–6.PubMedCrossRef
38.
Mohan BP, How G, Loh Y, Linn YC. Sorafenib monotherapy gives sustainable suppression of FLT3 clone in untreated patients with FLT3-internal tandem duplication positive acute myeloid Leukaemia. Br J Haematol. 2012;157:131–2.PubMedCrossRef
39.
Mori M, Sprague J. The successful remission induction by sorafenib and long-term complete remission in a FLT3-ITD-positive patient with a refractory acute erythroid leukemia and abnormal cytogenetics. Leuk Res. 2012;36:e1–3.PubMedCrossRef
40.
Safaian N, Czibere A, Bruns I, Fenk R, Reinecke P, Dienst A, 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.PubMedCrossRef
41.
Schroeder T, Zohren F, Saure C, Bruns I, Czibere A, Safaian NN, et al. Sorafenib treatment in 13 patients with acute myeloid leukemia and activating FLT3 mutations in combination with chemotherapy or as monotherapy. Acta Haematol. 2010;124:153–9.PubMedCrossRef
42.
Ravandi F, Yi CA, Cortes JE, Levis M, Faderl S, Garcia-Manero G, et al. Final report of phase II study of sorafenib, cytarabine, and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014;28:1543.PubMedPubMedCentralCrossRef
43.
Zhang QY, Wei XD, Yin QS, Mi RH, Yuan FF, Chen L. Sorafenib in combination with chemotherapy as first-line therapy for FLT3-ITD positive acute myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi. 2017;38:415-20.
44.
Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013;31:3110–8.PubMedCrossRef
45.
Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, et al. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017;1:331–40.PubMedPubMedCentralCrossRef
46.
Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015;16:1691–9.PubMedCrossRef
47.
Ravandi F, Alattar ML, Grunwald MR, Rudek MA, Rajkhowa T, Richie MA, 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.PubMedPubMedCentralCrossRef
48.
Brunner AM, Li S, Fathi AT, Wadleigh M, Ho VT, Collier K, et al. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol. 2016;175:496–504.PubMedPubMedCentralCrossRef
49.
Gallogly MM, Lazarus HM. Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016;7:73–83.PubMedPubMedCentral
50.
Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005;105:54–60.PubMedCrossRef
51.
Fischer T, Stone RM, DeAngelo DJ, Galinsky I, Estey E, Lanza C, 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.PubMedPubMedCentralCrossRef
52.
Stone RM, Fischer T, Paquette R, Schiller G, Schiffer CA, Ehninger G, 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.PubMedPubMedCentralCrossRef
53.
Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377:454–64.PubMedCrossRef
54.
Cooper BW, Kindwall-Keller TL, Craig MD, Creger RJ, Hamadani M, William WT, et al. A phase I study of midostaurin and azacitidine in relapsed and elderly AML patients. Clin Lymphoma Myeloma Leuk. 2015;15:428-32. e422.CrossRef
55.
Strati P, Kantarjian H, Ravandi F, Nazha A, Borthakur G, Daver N, et al. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Am J Hematol. 2015;90:276–81.PubMedPubMedCentralCrossRef
56.
Williams CB, Kambhampati S, Fiskus W, Wick J, Dutreix C, Ganguly S, 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.PubMedCrossRef
57.
Levis M. Quizartinib for the treatment of FLT3/ITD acute myeloid leukemia. Future Oncol. 2014;10:1571–9.PubMedCrossRef
58.
Cortes JE, Perl AE, Dombret H, Kayser S, Steffen B, Rousselot P, 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(ASH annual meeting abstracts). Blood. 2012;120:Abstract 48.
59.
Levis MJ, Perl AE, Dombret H, Döhner H, Steffen B, Rousselot P, 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(ASH annual meeting abstracts). Blood. 2012;120:Abstract 673.
60.
Cortes JE, Tallman MS, Schiller G, Trone D, Gammon G, Goldberg S, et al. Results of a phase 2 randomized, open-label, study of lower doses of quizartinib (AC220; ASP2689) in subjects with FLT3-ITD positive relapsed or refractory acute myeloid leukemia (AML) (ASH annual meeting abstracts). Blood. 2013;122:Abstract 494.
61.
Smith CC, Lasater EA, Lin KC, Wang Q, McCreery MQ, Stewart WK, et al. Crenolanib is a selective type I pan-FLT3 inhibitor. Proc Natl Acad Sci. 2014;111:5319–24.PubMedPubMedCentralCrossRef
62.
63.
Galanis A, Ma H, Rajkhowa T, Ramachandran A, Small D, Cortes J, et al. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014;123:94–100.PubMedPubMedCentralCrossRef
64.
Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, et al. Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood. 2017;129:257–60.PubMedCrossRef
65.
Hexner EO, Serdikoff C, Jan M, Swider CR, Robinson C, Yang S, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood. 2008;111:5663–71.PubMedPubMedCentralCrossRef
66.
Hexner EO, Mascarenhas J, Prchal J, Roboz GJ, Baer MR, Ritchie EK, et al. Phase I dose escalation study of lestaurtinib in patients with myelofibrosis. Leukemia Lymphoma. 2015;56:2543–51.PubMedPubMedCentralCrossRef
67.
Schlenk RF, Lübbert M, Benner A, Lamparter A, Krauter J, Herr W, et al. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Ann Hematol. 2016;95:1931–42.PubMedPubMedCentralCrossRef
68.
Nazha A, Bueso-Ramos C, Estey E, Faderl S, O'Brien S, Fernandez MH, et al. The addition of all-trans retinoic acid to chemotherapy may not improve the outcome of patient with NPM1 mutated acute myeloid leukemia. Front Oncol. 2013;3:218.PubMedPubMedCentralCrossRef
69.
Burnett AK, Hills RK, Green C, Jenkinson S, Koo K, Patel Y, et al. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA. Blood. 2010;115:948–56.PubMedCrossRef
70.
El Hajj H, Dassouki Z, Berthier C, Raffoux E, Ades L, Legrand O, et al. Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells. Blood. 2015;125:3447–54.PubMedCrossRef
71.
Martelli MP, Gionfriddo I, Mezzasoma F, Milano F, Pierangeli S, Mulas F, et al. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells. Blood. 2015;125:3455–65.PubMedCrossRef
72.
De Propris MS, Raponi S, Diverio D, Milani ML, Meloni G, Falini B, et al. High CD33 expression levels in acute myeloid leukemia cells carrying the nucleophosmin (NPM1) mutation. Haematologica. 2011;96:1548–51.PubMedPubMedCentralCrossRef
73.
Falini B, Brunetti L, Martelli MP. Dactinomycin in NPM1-mutated acute myeloid leukemia. N Engl J Med. 2015;373:1180–2.PubMedCrossRef
74.
Celik H, Mallaney C, Kothari A, Ostrander EL, Eultgen E, Martens A, et al. Enforced differentiation of Dnmt3a-null bone marrow leads to failure with c-Kit mutations driving leukemic transformation. Blood. 2015;125:619–28.PubMedPubMedCentralCrossRef
75.
Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, 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. 2009;28:562–9.PubMedCrossRef
76.
Issa J-PJ, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood. 2004;103:1635–40.PubMedCrossRef
77.
Blum W, Klisovic RB, Hackanson B, Liu Z, Liu S, Devine H, et al. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol. 2007;25:3884–91.PubMedCrossRef
78.
Cashen AF, Schiller GJ, O'Donnell MR, DiPersio JF. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2009;28:556–61.PubMedCrossRef
79.
Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci. 2010;107:7473–8.PubMedPubMedCentralCrossRef
80.
Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375:2023–36.PubMedPubMedCentralCrossRef
81.
Issa J-PJ, Roboz G, Rizzieri D, Jabbour E, Stock W, O'Connell C, et al. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 2015;16:1099–110.PubMedPubMedCentralCrossRef
82.
83.
Kantarjian H, Faderl S, Garcia-Manero G, Luger S, Venugopal P, Maness L, et al. Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study. Lancet Oncol. 2012;13:1096–104.PubMedPubMedCentralCrossRef
84.
Yen K, Travins J, Wang F, David MD, Artin E, Straley K, et al. AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations. Cancer Discovery. 2017;7:478–93.PubMedCrossRef
85.
Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Goerlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128:686–98.PubMedCrossRef
86.
Fan B, Le K, Manyak E, Liu H, Prahl M, Bowden CJ, et al. Longitudinal pharmacokinetic/pharmacodynamic profile of AG-120, a potent inhibitor of the IDH1 mutant protein, in a phase 1 study of IDH1-mutant advanced hematologic malignancies (ASH annual meeting abstracts). Blood. 2015;126:Abstract 1310.
87.
Shih AH, Meydan C, Shank K, Garrett-Bakelman FE, Ward PS, Intlekofer AM, et al. Combination targeted therapy to disrupt aberrant oncogenic signaling and reverse epigenetic dysfunction in IDH2-and TET2-mutant acute myeloid leukemia. Cancer Discovery. 2017;7:494–505.PubMedCrossRef
88.
89.
Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, et al. Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. J Clin Oncol. 2012;30:2204–10.PubMedPubMedCentralCrossRef
90.
Lübbert M, Kuendgen A. Combining DNA methyltransferase and histone deacetylase inhibition to treat acute myeloid leukemia/myelodysplastic syndrome: achievements and challenges. Cancer. 2015;121:498–501.PubMedCrossRef
91.
Kirschbaum M, Gojo I, Goldberg SL, Bredeson C, Kujawski LA, Yang A, et al. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. Br J Haematol. 2014;167:185–93.PubMedCrossRef
92.
Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, 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;121:556–61.PubMedCrossRef
93.
Prebet T, Sun Z, Figueroa ME, Ketterling R, Melnick A, Greenberg PL, et al. Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US leukemia intergroup trial E1905. J Clin Oncol. 2014;32:1242–8.PubMedPubMedCentralCrossRef
94.
Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121:4854–60.PubMedPubMedCentralCrossRef
95.
Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2010;29:369–77.PubMedCrossRef
96.
Lichtenegger FS, Krupka C, Köhnke T, Subklewe M. Immunotherapy for acute myeloid leukemia. Semin Hematol. 2015;52:207–14.PubMedCrossRef
97.
Hills RK, Castaigne S, Appelbaum FR, Delaunay J, Petersdorf S, Othus M, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014;15:986–96.PubMedPubMedCentralCrossRef
98.
99.
Walter RB, Raden BW, Kamikura DM, Cooper JA, Bernstein ID. Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity. Blood. 2005;105:1295–302.PubMedCrossRef
100.
Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, et al. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013;122:3432–9.PubMedPubMedCentralCrossRef
101.
Kurimoto M, Matsuoka H, Hanaoka N, Uneda S, Murayama T, Sonoki T, et al. Pretreatment of leukemic cells with low-dose decitabine markedly enhances the cytotoxicity of gemtuzumab ozogamicin. Leukemia. 2013;27:233–5.PubMedCrossRef
102.
Fathi AT, Erba HP, Lancet JE, Stein EM, Walter RB, DeAngelo DJ, et al. SGN-CD33A plus hypomethylating agents: a novel, well-tolerated regimen with high remission rate in frontline unfit AML (ASH annual meeting abstracts). Blood. 2015;126:Abstract 454.CrossRef
103.
Bixby DL, Stein AS, Fathi AT, Kovacsovics TJ, Levy MY, Erba HP, et al. Vadastuximab talirine monotherapy in older patients with treatment naive CD33-positive acute myeloid leukemia (AML) (ASH annual meeting abstracts). Blood. 2016;128:Abstract 590.
104.
Frankel AE, Konopleva M, Hogge D, Rizzieri D, Brooks C, Cirrito T, et al. Activity and tolerability of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk, as a single agent in patients with advanced hematologic malignancies. J Clin Oncol. 2013;31:7029.
105.
Lee EM, Yee D, Busfield SJ, McManus JF, Cummings N, Vairo G, et al. Efficacy of an Fc-modified anti-CD123 antibody (CSL362) combined with chemotherapy in xenograft models of acute myelogenous leukemia in immunodeficient mice. Haematologica. 2015;100:914–26.PubMedPubMedCentralCrossRef
106.
Duval M, Klein JP, He W, Cahn J-Y, Cairo M, Camitta BM, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730–8.PubMedPubMedCentralCrossRef
107.
Barrett DM, Singh N, Porter DL, Grupp SA, June CH. Chimeric antigen receptor therapy for cancer. Annu Rev Med. 2014;65:333–47.PubMedCrossRef
108.
109.
Fan M, Li M, Gao L, Geng S, Wang J, Wang Y, et al. Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. J Hematol Oncol. 2017;10:151.PubMedPubMedCentralCrossRef
110.
Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014;123:2343–54.PubMedPubMedCentralCrossRef
111.
Kenderian S, Ruella M, Shestova O, Klichinsky M, Aikawa V, Morrissette J, et al. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia. 2015;29:1637–47.PubMedPubMedCentralCrossRef
112.
Pizzitola I, Anjos-Afonso F, Rouault-Pierre K, Lassailly F, Tettamanti S, Spinelli O, et al. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia. 2014;28:1596–605.PubMedCrossRef
113.
114.
115.
Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114:1545–52.PubMedPubMedCentralCrossRef
116.
Albring J, Inselmann S, Sauer T, Schliemann C, Altvater B, Kailayangiri S, et al. PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation. Bone Marrow Transplant. 2017;52:317–20.PubMedCrossRef
117.
Metadata
Title
Precision therapy for acute myeloid leukemia
Authors
Xue Yang
Jianxiang Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0543-7

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