Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

doi:10.1186/s40364-019-0170-2

Review

. 2019 Sep 11:7:19.

doi: 10.1186/s40364-019-0170-2. eCollection 2019.

Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

Juanjuan Zhao¹, Yongping Song¹, Delong Liu^{1

2}

Affiliations

¹ 1Department of Oncology, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
² 2Division of Hematology & Oncology, New York Medical College, Valhalla, NY 10595 USA.

PMID: 31528345
PMCID: PMC6737601
DOI: 10.1186/s40364-019-0170-2

Review

Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

Juanjuan Zhao et al. Biomark Res. 2019.

. 2019 Sep 11:7:19.

doi: 10.1186/s40364-019-0170-2. eCollection 2019.

Authors

Juanjuan Zhao¹, Yongping Song¹, Delong Liu^{1

2}

Affiliations

¹ 1Department of Oncology, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
² 2Division of Hematology & Oncology, New York Medical College, Valhalla, NY 10595 USA.

PMID: 31528345
PMCID: PMC6737601
DOI: 10.1186/s40364-019-0170-2

Erratum in

Correction to: Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia.
Zhao J, Song Y, Liu D. Zhao J, et al. Biomark Res. 2019 Oct 17;7:21. doi: 10.1186/s40364-019-0172-0. eCollection 2019. Biomark Res. 2019. PMID: 31636908 Free PMC article.

Abstract

FMS-like tyrosine kinase 3- internal tandem duplication (FLT3-ITD) remains as one of the most frequently mutated genes in acute myeloid leukemia (AML), especially in those with normal cytogenetics. The FLT3-ITD and FLT3-TKD (tyrosine kinase domain) mutations are biomarkers for high risk AML and are associated with drug resistance and high risk of relapse. Multiple FLT3 inhibitors are in clinical development, including lestaurtinib, tandutinib, quizartinib, midostaurin, gilteritinib, and crenolanib. Midostaurin and gilteritinib have been approved by FDA for Flt3 mutated AML. Gilteritinib (ASP2215, Xospata) is a small molecule dual inhibitor of FLT3/AXL. The ADMIRAL study showed that longer overall survival and higher response rate are associated with gilteritinib in comparison with salvage chemotherapy for relapse /refractory (R/R) AML. These data from the ADMIRAL study may lead to the therapy paradigm shift and establish gilteritinib as the new standard therapy for R/R FLT3-mutated AML. Currently, multiple clinical trials are ongoing to evaluate the combination of gilteritinib with other agents and regimens. This study summarized clinical trials of gilteritinib for AML.

Keywords: FLT3; FLT3 inhibitor; Gilteritinib; Tyrosine kinase inhibitor.

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Conflict of interest statement

DL serves on the Xospata speaker bureau of Astellas. Astellas was not involved in this publication.

Figures

**Fig. 1**
The ADMIRAL study scheme. The ADMIRAL study is an open-label multicenter randomized phase 3 study for adults with relapsed and/or refractory AML with FLT3 mutations. The randomization between gilteritinib and one of the four salvage chemotherapy regimens was 2:1. To date, the accrual has been completed with 371 patients randomized. MEC: mitoxantrone, etoposide, cyclophosphamide; FLAG-IDA: fludarabine, cytarabine, GCSF, idarubicin; CR/CRh: complete remission with partial hematologic recovery; OS: overall survival

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References

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[1] Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–2506. - PMC - PubMed

[2] Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–2506. - PMC - PubMed

[3] Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Döhner K, Schlenk RF, Döhner H, Campbell PJ. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221. - PMC - PubMed

[4] Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Döhner K, Schlenk RF, Döhner H, Campbell PJ. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221. - PMC - PubMed

[5] Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MRM, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–1089. - PMC - PubMed

[6] Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MRM, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–1089. - PMC - PubMed

[7] Wei H, Wang Y, Zhou C, Lin D, Liu B, Liu K, Qiu S, Gong B, Li Y, Zhang G, Wei S, Gong X, Liu Y, Zhao X, Gu R, Mi Y, Wang J. Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and eastern Asian population. J Hematol Oncol. 2018;11(1):18. - PMC - PubMed

[8] Wei H, Wang Y, Zhou C, Lin D, Liu B, Liu K, Qiu S, Gong B, Li Y, Zhang G, Wei S, Gong X, Liu Y, Zhao X, Gu R, Mi Y, Wang J. Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and eastern Asian population. J Hematol Oncol. 2018;11(1):18. - PMC - PubMed

[9] Yang J. SALL4 as a transcriptional and epigenetic regulator in normal and leukemic hematopoiesis. Biomarker Res. 2018;6(1):1. - PMC - PubMed

[10] Yang J. SALL4 as a transcriptional and epigenetic regulator in normal and leukemic hematopoiesis. Biomarker Res. 2018;6(1):1. - PMC - PubMed

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Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

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Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

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