An update of current treatments for adult acute myeloid leukemia

Lo-Coco, 2013, Retinoic acid and arsenic trioxide for acute promyelocytic leukemia., N Engl J Med, 369, 111, 10.1056/NEJMoa1300874 Fernandez, 2009, Anthracycline dose intensification in acute myeloid leukemia., N Engl J Med, 361, 1249, 10.1056/NEJMoa0904544 Luskin, 2014, High dose daunorubicin improves survival in AML up to age 60, across all cytogenetic risk groups including patients with unfavorable cytogenetic risk and FLT3-ITD mutant AML: updated analysis from Eastern Cooperative Oncology Trial E1900 [abstract]., Blood, 124, 10.1182/blood.V124.21.373.373 Löwenberg, 2009, High-dose daunorubicin in older patients with acute myeloid leukemia., N Engl J Med, 361, 1235, 10.1056/NEJMoa0901409 Lee, 2011, A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia., Blood, 118, 3832, 10.1182/blood-2011-06-361410 Burnett, 2015, A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients., Blood, 125, 3878, 10.1182/blood-2015-01-623447 Pautas, 2010, Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia aged 50 to 70 years: Results of the ALFA-9801 Study., J Clin Oncol, 28, 808, 10.1200/JCO.2009.23.2652 Ohtake, 2011, Randomized trial of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study., Blood, 117, 2358, 10.1182/blood-2010-03-273243 Döhner, 2010, Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet., Blood, 115, 453, 10.1182/blood-2009-07-235358 Weick, 1996, A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study., Blood, 88, 2841, 10.1182/blood.V88.8.2841.bloodjournal8882841 Bishop, 1996, Randomized study of high-dose cytarabine in induction in acute myeloid leukemia., Blood, 87, 1710, 10.1182/blood.V87.5.1710.1710 Löwenberg, 2011, Cytarabine dose for acute myeloid leukemia., N Engl J Med, 364, 1027, 10.1056/NEJMoa1010222 Willemze, 2014, 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, 32, 219, 10.1200/JCO.2013.51.8571 Büchner, 2012, Acute myeloid leukemia (AML): different treatment strategies versus a common standard arm: combined prospective analysis by the German AML Intergroup., J Clin Oncol, 30, 3604, 10.1200/JCO.2012.42.2907 Karp, 1989, In vivo cell growth and pharmacologic determinants of clinical response in acute myelogeneous leukemia., Blood, 73, 24, 10.1182/blood.V73.1.24.24 Castaigne, 2004, Randomized comparison of double induction and timed-sequential induction to a « 3+7 » induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study., Blood, 104, 2467, 10.1182/blood-2003-10-3561 Büchner, 2006, Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and post-remission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia., J Clin Oncol, 24, 2480, 10.1200/JCO.2005.04.5013 Braess, 2009, Dose-dense induction with sequential high-dose cytarabine and mitoxantrone (S-HAM) and pelfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG., Blood, 113, 3903, 10.1182/blood-2008-07-162842 Petersdorf, 2013, A Phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia., Blood, 121, 4854, 10.1182/blood-2013-01-466706 Burnett, 2011, Identification of patients with acute myeloid leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial., J Clin Oncol, 29, 369, 10.1200/JCO.2010.31.4310 Burnett, 2012, Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia., J Clin Oncol, 30, 3924, 10.1200/JCO.2012.42.2964 Castaigne, 2012, Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study., Lancet, 379, 1508, 10.1016/S0140-6736(12)60485-1 Delaunay, 2011, Addition of gemtuzumab ozogamicin to chemotherapy improves event-free survival but not overall survival of AML patients with intermediate cytogenetics not eligible for allogeneic transplantation: results of the GOELAMS AML 2006 IR study [abstract]., Blood, 118, 10.1182/blood.V118.21.79.79 Burnett, 2014, A comparison of single-dose gemtuzumab ozogamicin 3 mg/m2 and 6 mg/m2 combined with induction chemotherapy in younger patients with AML: data from the UK NCRI AML17 trial [abstract]., Blood, 124, 10.1182/blood.V124.21.2308.2308 Amadori, 2013, Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17)., J Clin Oncol, 31, 4424, 10.1200/JCO.2013.49.0771 Löwenberg, 2010, Gemtuzumab ozogamicin as post-remission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study., Blood, 115, 2586, 10.1182/blood-2009-10-246470 Hills, 2014, 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, 15, 986, 10.1016/S1470-2045(14)70281-5 Holowiecki, 2012, 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, 30, 2441, 10.1200/JCO.2011.37.1286 Russell, 2015, A comparison of daunorubicin/ara-c versus daunorubicin/clofarabine as induction treatment in older patients with AML and high-risk MDS: Long term results of the UK NCRI AML16 trial in 806 patients [abstract]., Haematologica, 100 Burnett, 2013, Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial., J Clin Oncol, 31, 3360, 10.1200/JCO.2012.47.4874 Thomas, Clofarabine-based consolidation improves relapse-free survival of younger adults with non-favorable acute myeloid leukemia (AML) in first remission: results of the randomized ALFA-0702/CLARA study [abstract]., 10.1182/blood.V126.23.218.218 Faderl, 2012, Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial., J Clin Oncol, 30, 2492, 10.1200/JCO.2011.37.9743 Faderl, 2006, Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older., Blood, 108, 45, 10.1182/blood-2005-08-3294 Kantarjian, 2010, Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors., J Clin Oncol, 28, 549, 10.1200/JCO.2009.23.3130 Willemze, 2014, Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial)., Ann Hematol, 93, 965 Serve, 2013, Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial., J Clin Oncol, 31, 3110, 10.1200/JCO.2012.46.4990 Röllig, 2014, Sorafenib versus placebo in addition to standard therapy in younger patients with newly diagnosed acute myeloid leukemia: results from 267 patients treated in the randomized placebo-controlled SAL-SORAML trial [abstract]., Blood, 124, 10.1182/blood.V124.21.6.6 Mayer, 1994, Intensive postremission chemotherapy in adults with acute myeloid leukemia., N Engl J Med, 331, 896, 10.1056/NEJM199410063311402 Löwenberg, 2013, Sense and nonsense of high-dose cytarabine for acute myeloid leukemia., Blood, 121, 26, 10.1182/blood-2012-07-444851 Schlenk, 2014, Post-remission therapy for acute myeloid leukemia., Haematologica, 99, 1663, 10.3324/haematol.2014.114611 Cornelissen, 2007, Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom?, Blood, 109, 3658, 10.1182/blood-2006-06-025627 Koreth, 2009, Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials., JAMA, 301, 2349, 10.1001/jama.2009.813 Schlenk, 2008, Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia., N Engl J Med, 358, 1909, 10.1056/NEJMoa074306 Gooley, 2010, Reduced mortality after allogeneic hematopoietic-cell transplantation., N Engl J Med, 363, 2091, 10.1056/NEJMoa1004383 Luznik, 2012, Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation., Semin Oncol, 39, 683, 10.1053/j.seminoncol.2012.09.005 Ciurea, 2015, Haploidentical transplant with post-transplant cyclophosphamide versus matched unrelated donor transplant for acute myeloid leukemia., Blood, 126, 1033, 10.1182/blood-2015-04-639831 Russell, 2015, A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia., Leukemia, 29, 1478, 10.1038/leu.2014.319 Lioure, 2012, Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study., Blood, 119, 2943, 10.1182/blood-2011-05-352989 Cornelissen, 2015, Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years., Leukemia, 29, 1041, 10.1038/leu.2014.332 Passweg, 2015, Conditioning intensity in middle-aged patients with AML in first CR: no advantage for myeloablative regimens irrespective of the risk group-an observational analysis by the Acute Leukemia Working Party of the EBMT., Bone Marrow Transplant, 50, 1063, 10.1038/bmt.2015.121 Brunet, 2013, Hematopoietic transplantation for acute myeloid leukemia with internal tandem duplication of FLT3 gene (FLT3/ITD)., Curr Opin Oncol, 25, 195, 10.1097/CCO.0b013e32835ec91f Pratcorona, 2013, Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy., Blood, 121, 2734, 10.1182/blood-2012-06-431122 Linch, 2014, Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia., Blood, 124, 273, 10.1182/blood-2014-02-554667 Schlenk, 2014, Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation., Blood, 124, 3441, 10.1182/blood-2014-05-578070 Grimwade, 2014, Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?, Blood, 124, 3345, 10.1182/blood-2014-05-577593 Kayser, 2015, Minimal residual disease in acute myeloid leukemia–current status and future perspectives., Curr Hematol Malig Rep, 10, 132, 10.1007/s11899-015-0260-7 Chen, 2015, Relation of clinical response and minimal residual disease and their prognostic impact on outcome in acute myeloid leukemia., J Clin Oncol, 33, 1258, 10.1200/JCO.2014.58.3518 Jourdan, 2013, Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia., Blood, 121, 2213, 10.1182/blood-2012-10-462879 Walter, 2013, Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission., Blood, 122, 1813, 10.1182/blood-2013-06-506725 Boissel, 2015, Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial., Haematologica, 100, 780, 10.3324/haematol.2014.114884 Paschka, 2015, Dasatinib (DAS) in combination with chemotherapy and as maintenance in core-binding factor (CBF) acute myeloid leukemia (AML): a phase Ib/IIa study of the German-Austrian AML Study Group (AMLSG) [abstract]., Haematologica, 100 Marcucci, 2014, Adding KIT inhibitor dasatinib (DAS) to chemotherapy overcomes the negative impact of KIT mutation/over-expression in core binding factor (CBF) acute myeloid leukemia (AML): results from CALGB 10801 (Alliance) [abstract]., Blood, 124, 10.1182/blood.V124.21.8.8 Levis, 2011, Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse., Blood, 117, 3294, 10.1182/blood-2010-08-301796 Knapper, 2014, A randomised comparison of the sequential addition of the FLT3 inhibitor lestaurtinib (CEP701) to standard first line chemotherapy for FLT3-mutated acute myeloid leukemia: The UK experience [abstract]., Blood, 124, 10.1182/blood.V124.21.3736.3736 Chen, 2014, Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for patients with FLT3-ITD AML [abstract]., Blood, 124, 10.1182/blood.V124.21.671.671 Daver, 2015, Secondary mutations as mediators of resistance to targeted therapy in leukemia., Blood, 125, 3236, 10.1182/blood-2014-10-605808 Burnett, 2010, 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, 115, 948, 10.1182/blood-2009-08-236588 Schlenk, 2009, Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG trial AML HD98B., Haematologica, 94, 54, 10.3324/haematol.13378 Schlenk, 2011, All-trans retinoic acid improves outcome in younger patients with nucleophosmin-1 mutated acute myeloid leukemia. Results of the AMLSG 07-04 randomized treatment trial [abstract]., Blood, 118, 10.1182/blood.V118.21.80.80 El Hajj, 2015, Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells., Blood, 125, 3447, 10.1182/blood-2014-11-612416 Martelli, 2015, Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells., Blood, 125, 3455, 10.1182/blood-2014-11-611459 Jaglal, 2014, Cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) compared to standard induction in acute myeloid leukemia from myelodysplastic syndrome after azanucleoside failure., Leuk Res, 38, 443, 10.1016/j.leukres.2013.12.010 Stone, 2015, Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia., J Clin Oncol, 33, 1252, 10.1200/JCO.2014.57.0952 Genovese, 2014, Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence., N Engl J Med, 371, 2477, 10.1056/NEJMoa1409405 Jaiswal, 2014, Age-related clonal hematopoiesis associated with adverse outcomes., N Engl J Med, 371, 2488, 10.1056/NEJMoa1408617 Becker, 2010, Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study., J Clin Oncol, 28, 596, 10.1200/JCO.2009.25.1496 Gardin, 2013, Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older., J Clin Oncol, 31, 321, 10.1200/JCO.2011.40.3642 Burnett, 2007, A comparison of low-dose cytarabine and hydoxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment., Cancer, 109, 1114, 10.1002/cncr.22496 Kantarjian, 2012, 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, 30, 2670, 10.1200/JCO.2011.38.9429 Dombret, 2015, International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts., Blood, 126, 291, 10.1182/blood-2015-01-621664 Burnett, 2012, The addition of the farnesyl transferase inhibitor, tipifarnib, to low dose cytarabine does not improve outcome for older patients with AML., Br J Haematol, 158, 519, 10.1111/j.1365-2141.2012.09165.x Burnett, 2011, The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome., Leukemia, 25, 1122, 10.1038/leu.2011.59 Burnett, 2013, The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison., Leukemia, 27, 75, 10.1038/leu.2012.229 Dennis, 2015, Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia., Blood, 125, 2923, 10.1182/blood-2014-10-608117 Burnett, 2015, A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia., Leukemia, 29, 1312, 10.1038/leu.2015.38 Burnett, 2013, Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival., Blood, 122, 1384, 10.1182/blood-2013-04-496596 Döhner, 2014, Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy., Blood, 124, 1426, 10.1182/blood-2014-03-560557 Naval, 2014, Phase I/II study of vosaroxin and decitabine in newly diagnosed older patients (pts) with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) [abstract]., Blood, 124, 10.1182/blood.V124.21.385.385 Breems, 2005, Prognostic index for adult patients with acute myeloid leukemia in first relapse., J Clin Oncol, 23, 1969, 10.1200/JCO.2005.06.027 Burnett, 2013, Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission., J Clin Oncol, 31, 1293, 10.1200/JCO.2011.40.5977 Ravandi, 2014, Improved survival in patients with first relapsed or refractory acute myeloid leukemia (AML) treated with vosaroxin plus cytarabine versus placebo plus cytarabine: results of a phase 3 double-blind randomized controlled multinational study (VALOR) [abstract]., Blood, 124, 10.1182/blood.V124.21.LBA-6.LBA-6 O’Donnell, 2012, Acute myeloid leukemia., J Natl Compr Canc Netw, 10, 984, 10.6004/jnccn.2012.0103