2,472
Views
15
CrossRef citations to date
0
Altmetric
Review

Novel therapies for AML: a round-up for clinicians

ORCID Icon &
Pages 1389-1400 | Received 13 Sep 2020, Accepted 09 Nov 2020, Published online: 07 Jan 2021

References

  • Siegel R, Miller K, Ahmedin J. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan 01;68(1):7–30.
  • Siegel R, Miller K, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan 01;70(1):7–30.
  • Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011 Feb 10;29(5):487–494.
  • Gilliland D, Griffin J. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002 Sep 01;100(5):1532–1542.
  • 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 Dec 15;100(13):4372–4380.
  • Kottaridis P, Gale R, Frew M, 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 Sep 15;98(6):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 Jul 1;100(1):59–66.
  • **Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728–1740. .
  • 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 Jun 6;121(23):4655–4662.
  • Fiedler W, Kayser S, Kebenko M, et al. A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations. Br J Haematol. 2015 Jun;169(5):694–700. .
  • Pratz KW, Cortes J, Roboz GJ, et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009 Apr 23;113(17):3938–3946.
  • Smith B, Levis M, Beran M, et al. Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood. 2004 May 15;103(10):3669–3676.
  • Stone R, DeAngelo D, Klimek V, 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 Jan 1;105(1):54–60.
  • Swaminathan M, Kantarjian HM, Daver N, et al. The combination of quizartinib with azacitidine or low dose cytarabine is highly active in patients (Pts) with FLT3-ITD mutated myeloid leukemias: interim report of a phase I/II trial. Blood. 2017;130(Supplement 1):723.
  • Wang E, Tallman M, Stone R, et al. Low relapse rate in younger patients ≤ 60 years old with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) treated with crenolanib and cytarabine/anthracycline chemotherapy. Blood. 2017;130(Supplement 1):566.
  • **Stone R, Mandrekar S, Sanford B, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454–464. .
  • Antar A, Otrock Z, El-Cheikh J, et al. Inhibition of FLT3 in AML: a focus on sorafenib. Bone Marrow Transplant. 2017 Mar 01;52(3):344–351.
  • Röllig C, Serve H, Hüttmann A, 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 Dec 01;16(16):1691–1699.
  • Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020 Sep 10;38(26):2993–3002.
  • Mardis E, Ding L, Dooling D, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009 Sep 10;361(11):1058–1066.
  • Ward P, Patel J, Wise D, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010 Mar 01;17(3):225–234.
  • Galkin M, Jonas BA. Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy. Core Evid. 2019;14:3–17. .
  • Golub D, Iyengar N, Dogra S, et al. Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics. Front Oncol. 2019 May 17;9.
  • Fathi A, Dinardo C, Kline I, et al. Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2. JAMA Oncol. 2018 Aug 01;4(8):1106.
  • **Dinardo C, Stein E, Botton S, et al. Durable remissions with ivosidenib inIDH1-mutated relapsed or refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386–2398. .
  • Roboz G, Dinardo C, Stein E, et al. Ivosidenib (IVO; AG-120) in IDH1-mutant newly-diagnosed acute myeloid leukemia (ND AML): updated results from a phase 1 study. J Clin Oncol. 2019;37(15_suppl):7028. .
  • Dinardo C, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 03;133(1):7–17.
  • Stein E, Dinardo C, Pollyea D, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug 10;130(6):722–731.
  • **Stein E, Dinardo C, Fathi A, et al. Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib. Blood. 2019 Feb 14;133(7):676–687. .
  • Pollyea D, Tallman M, De Botton S, et al. Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia. Leukemia. 2019 Nov 01;33(11):2575–2584.
  • Zhao C, Chen A, Jamieson C, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 2009 Apr 01;458(7239):776–779.
  • *Cortes J, Smith B, Wang E, et al. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: phase 2 study results. Am J Hematol. 2018 Nov 01;93(11):1301–1310. .
  • Campbell V, Copland M. Hedgehog signaling in cancer stem cells: a focus on hematological cancers. Stem Cells Cloning. 2015;8:27–38.
  • Cortes J, Heidel FH, Hellmann A, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379–389. .
  • Adams J, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007 Feb 01;26(9):1324–1337.
  • Konopleva M, Pollyea D, Potluri J, et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 2016 Oct 01;6(10):1106–1117.
  • Wei A, Strickland S, Hou J, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277–1284.
  • Dinardo C, Pratz K, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb 01;19(2):216–228.
  • Pollyea DA, Amaya M, Strati P, et al. Venetoclax for AML: changing the treatment paradigm. Blood Adv. 2019 Dec 23;3(24):4326–4335.
  • **Dinardo C, Jonas B, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020 Oct 13;383(7):617–629. .
  • *Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137–2145. .
  • Aldoss I, Yang D, Aribi A, et al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica. 2018 Sep;103(9):e404–e407. .
  • Agarwal S, Dinardo C, Potluri J, et al. Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin Ther. 2017 Feb 01;39(2):359–367.
  • Dinardo C, Rausch C, Benton C, et al. Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol. 2018 Mar 01;93(3):401–407.
  • Baron J, Wang ES. Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia. Expert Rev Clin Pharmacol. 2018 Jun;11(6):549–559.
  • Castaigne S, Pautas C, Terré C, et al. 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. 2012 Mar 01;379(9825):1508–1516.
  • *Lambert J, Pautas C, Terre C, et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113–119. .
  • Burnett A, Hills R, Milligan D, 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. 2011 Feb 01;29(4):369–377.
  • Hills R, Castaigne S, Appelbaum F, 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 Aug;15(9):986–996. .
  • Amadori S, Suciu S, Selleslag D, et al. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972–979.
  • Taksin A, Legrand O, Raffoux E, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan 01;21(1):66–71.
  • **Lancet J, Uy G, Cortes J, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684–2692. .
  • **Wei AH, Döhner H, Pocock C, et al. The QUAZAR AML-001 maintenance trial: results of a phase iii international, randomized, double-blind, placebo-controlled study of CC-486 (oral formulation of azacitidine) in patients with acute myeloid leukemia (AML) in first remission. Blood. 2019;134(Supplement_2): LBA-3-LBA–3. .
  • Wang ES. Beyond midostaurin: which are the most promising FLT3 inhibitors in AML? Best Pract Res Clin Haematol. 2019 Dec;32(4):101103.
  • Luger S, Sun Z, Loghavi S, et al. Phase II randomized trial of gilteritinib vs. midostaurin in newly diagnosed FLT3 mutated acute myeloid leukemia (AML). Blood. 2019;134(Supplement 1):1309. .
  • Ferrara F. Venetoclax plus hypomethylating agents or low-dose cytarabine in acute myeloid leukemia: all that glitters is gold? Blood Cancer J. 2020 Jan 28;10(1):10.
  • Aboudalle I, Konopleva MY, Kadia TM, et al. A phase Ib/II study of the BCL-2 inhibitor venetoclax in combination with standard intensive AML induction/consolidation therapy with FLAG-IDA in patients with newly diagnosed or relapsed/refractory AML. Blood. 2019;134(Supplement_1):176. .
  • Cluzeau T, Sebert M, Rahmé R, et al. APR-246 combined with azacitidine (AZA) in TP53 mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). a phase 2 study by the groupe francophone des myélodysplasies (GFM). Blood. 2019;134(Supplement_1):677. .
  • Trudel G, Howes A, Jeste N, et al. CULMINATE: A phase II study of cusatuzumab + azacitidine in patients with newly diagnosed AML, ineligible for intensive chemotherapy. J Clin Oncol. 2020;38(15_suppl):TPS7565–TPS7565. .
  • Ravandi F, Stein AS, Kantarjian HM, et al. A phase 1 first-in-human study of AMG 330, an anti-CD33 bispecific T-cell engager (BiTE®) antibody construct, in relapsed/refractory acute myeloid leukemia (R/R AML). Blood. 2018;132(Supplement 1):25. .
  • Sallman D, Donnellan W, Asch A, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: initial phase 1b results. J Clin Oncol. 2019;37(15_suppl):7009. .
  • McGeehan J A first-in-class Menin-MLL1 antagonist for the treatment of MLL-r and NPM1 mutant leukemias [Oral abstract DDT01–01]. American Association for Cancer Research Virtual Annual Meeting I. 2020 Apr 27.

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.