Novel Agents for Acute Myeloid Leukemia

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2018 Nov 15

PMID 30423907

Citations 18

Authors

Mario Luppi

Francesco Fabbiano

Giuseppe Visani

Giovanni Martinelli

Adriano Venditti

Affiliations

Soon will be listed here.

Abstract

Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. Recent advances in the understanding of AML pathogenesis have paved the way for the development of new agents targeting specific molecules or mechanisms that contribute to finally move beyond the current standard of care, which is "3 + 7" regimen. In particular, new therapeutic options such as targeted therapies (midostaurin and enasidenib), monoclonal antibodies (gemtuzumab ozogamicin), and a novel liposomal formulation of cytarabine and daunorubicin (CPX-351) have been recently approved, and will be soon available for the treatment of adult patients with AML. In this review, we will present and describe these recently approved drugs as well as selected novel agents against AML that are currently under investigation, and show the most promising results as monotherapy or in combination with chemotherapy. The selection of these emerging treatments is based on the authors' opinion.

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References

Bose P, Grant S . Orphan drug designation for pracinostat, volasertib and alvocidib in AML. Leuk Res. 2014; 38(8):862-5. DOI: 10.1016/j.leukres.2014.06.007. View

Grunwald M, Levis M . FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol. 2013; 97(6):683-94. DOI: 10.1007/s12185-013-1334-8. View

Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S . Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients. Blood. 2007; 111(5):2527-37. DOI: 10.1182/blood-2007-05-091215. View

Altman J, Foran J, Pratz K, Trone D, Cortes J, Tallman M . Phase 1 study of quizartinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Am J Hematol. 2017; 93(2):213-221. PMC: 6586071. DOI: 10.1002/ajh.24974. View

Lim W, Tardi P, Xie X, Fan M, Huang R, Ciofani T . Schedule- and dose-dependency of CPX-351, a synergistic fixed ratio cytarabine:daunorubicin formulation, in consolidation treatment against human leukemia xenografts. Leuk Lymphoma. 2010; 51(8):1536-42. DOI: 10.3109/10428194.2010.490312. View

Perl A . The role of targeted therapy in the management of patients with AML. Blood Adv. 2018; 1(24):2281-2294. PMC: 5737125. DOI: 10.1182/bloodadvances.2017009829. View

Weisberg E, Boulton C, Kelly L, Manley P, Fabbro D, Meyer T . Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell. 2002; 1(5):433-43. DOI: 10.1016/s1535-6108(02)00069-7. View

Stein E, DiNardo C, Pollyea D, Fathi A, Roboz G, Altman J . Enasidenib in mutant relapsed or refractory acute myeloid leukemia. Blood. 2017; 130(6):722-731. PMC: 5572791. DOI: 10.1182/blood-2017-04-779405. View

DiNardo C, Stein E, de Botton S, Roboz G, Altman J, Mims A . Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018; 378(25):2386-2398. DOI: 10.1056/NEJMoa1716984. View

10.

Roboz G, Kantarjian H, Yee K, Kropf P, OConnell C, Griffiths E . Dose, schedule, safety, and efficacy of guadecitabine in relapsed or refractory acute myeloid leukemia. Cancer. 2017; 124(2):325-334. PMC: 5814873. DOI: 10.1002/cncr.31138. View

11.

Mehta S, Shukla S, Vora H . Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: its correlation with FLT3. Neoplasma. 2013; 60(6):666-75. DOI: 10.4149/neo_2013_085. View

12.

Zheng R, Friedman A, Small D . Targeted inhibition of FLT3 overcomes the block to myeloid differentiation in 32Dcl3 cells caused by expression of FLT3/ITD mutations. Blood. 2002; 100(12):4154-61. DOI: 10.1182/blood-2002-03-0936. View

13.

Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M . 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; 34(9):972-9. DOI: 10.1200/JCO.2015.64.0060. View

14.

Cortes J, Goldberg S, Feldman E, Rizzeri D, Hogge D, Larson M . Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2014; 121(2):234-42. PMC: 5542857. DOI: 10.1002/cncr.28974. View

15.

Albers C, Leischner H, Verbeek M, Yu C, Illert A, Peschel C . The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib. Leukemia. 2013; 27(6):1416-8. DOI: 10.1038/leu.2013.14. View

16.

Petersdorf S, Kopecky K, Slovak M, Willman C, Nevill T, Brandwein J . A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013; 121(24):4854-60. PMC: 3682338. DOI: 10.1182/blood-2013-01-466706. View

17.

Smith T, Temin S, Alesi E, Abernethy A, Balboni T, Basch E . American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol. 2012; 30(8):880-7. DOI: 10.1200/JCO.2011.38.5161. View

18.

Knapper S, Russell N, Gilkes A, Hills R, Gale R, Cavenagh J . A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML. Blood. 2016; 129(9):1143-1154. PMC: 5364440. DOI: 10.1182/blood-2016-07-730648. View

19.

Cortes J, Perl A, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T . Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018; 19(7):889-903. PMC: 8152787. DOI: 10.1016/S1470-2045(18)30240-7. View

20.

Zimmerman E, Turner D, Buaboonnam J, Hu S, Orwick S, Roberts M . Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia. Blood. 2013; 122(22):3607-15. PMC: 3837509. DOI: 10.1182/blood-2013-07-513044. View