Blood Res 2022; 57(S1): S32-S36
FLT3 mutations in acute myeloid leukemia: a review focusing on clinically applicable drugs
Jae-Sook Ahn1,2, Hyeoung-Joon Kim1,2
1Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University, Gwangju,
2Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Korea
Correspondence to: Jae-Sook Ahn, M.D., Ph.D.
Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Hwasun 58128, Korea
Received: January 19, 2022; Revised: February 28, 2022; Accepted: February 28, 2022; Published online: April 30, 2022.
© The Korean Journal of Hematology. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
FMS-like tyrosine kinase 3 (FLT3) mutations, the most frequently detected genetic aberrations in patients with acute myeloid leukemia (AML), are identified in approximately 30% of patients with newly diagnosed AML and are more common in patients with normal karyotypes. Since the discovery of FLT3 mutations in AML, clinical trials have been actively conducted in patients with FLT3 mutated AML, and FLT3 inhibitors have been introduced into clinical practice. The current standard treatment for patients with newly diagnosed FLT3-mutated AML is 7+3 induction chemotherapy combined with midostaurin. Additionally, gilteritinib is more effective than salvage chemotherapy for relapsed or refractory FLT3-mutated AML. Ongoing trials are expected to provide additional treatment options depending on the disease state and patient vulnerability. This review summarizes information on clinically available FLT3 inhibitors for the management of AML with FLT3 mutations.
Keywords: Acute myeloid leukemia, FLT3-ITD, FLT3-TKD, Tyrosine kinase inhibitor, Gilteritinib, Midostaurin

Acute myeloid leukemia (AML), the most common type of acute leukemia in adults, is characterized by poor prognosis, with a 5-year overall survival (OS) of 35% and less than 10% in patients over 65 years of age [1]. Approximately 1,300 patients are diagnosed with AML annually in South Korea [1]. In recent decades, clonal chromosomal aberrations and molecular mutations have been recognized as the most important prognostic markers in AML [2-4]. FMS-like tyrosine kinase 3 (FLT3) mutations, the most commonly observed genetic aberrations in patients with AML, are identified in approximately 30% of patients with newly diagnosed AML and are more frequently observed in patients with normal karyotypes. Since 1996, when the FLT3 internal tandem duplication (ITD) mutation was first identified in AML, numerous studies have been conducted regarding its relevance in prognosis [4-6]. Moreover, several advances have been made in targeting FLT3 mutations, and currently, FLT3 inhibitors are actively used in clinical practice [7-12]. In this review, we summarize information on clinically available FLT3 inhibitors for the management of AML with FLT3 mutations.


FLT3 transcribes FLT3 transmembrane receptor tyrosine kinase. It is usually expressed in marrow stromal cells and hematopoietic cells and is activated by the FLT3 ligand. FLT3 plays a key role in hematopoietic cell maturation and proliferation [13, 14]. FLT3 mutations lead to the activation of tyrosine kinase by initiating FLT3 ligand-independent dimerization activation, which results in aberrant proliferation of leukemic cells.

FLT3 mutations are heterogeneous in terms of their load, size, and location [15], and are divided into two classes: ITD involving the juxtamembrane domain and that involving the tyrosine kinase domain (TKD). FLT3-ITD leads to a gain-of-function by inhibiting the negative regulatory function of the juxtamembrane domain [16, 17]. FLT3-TKD mutations are point mutations in the activation loop of FLT3, mainly represented by codon D835 or deletion of codon I836, which leads to a loss of auto-inhibition [18]. Both mutations lead to the activation of downstream proliferation cascades [19, 20].

FLT3-ITD has a poor prognostic impact in patients with AML at diagnosis. However, FLT3-TKD mutations have not been associated with AML prognosis [4]. Owing to its prognostic significance and the choice of tyrosine kinase inhibitors, the European LeukemiaNet (ELN) recommends including molecular genetic testing for mutations of FLT3, both for ITD with allelic ratio and TKD, at diagnostic workup [4]. Testing for FLT3 mutations at relapse is also necessary because acquisition or loss of FLT3 mutations occurs due to clonal evolution in 20% of patients with relapsed AML [21, 22]. Rapid assays to identify FLT3 mutations are essential for the use of FLT3-targeting agents [4, 7, 23]. Clinically available assays include FLT3 polymerase chain reaction (PCR) and targeted DNA next-generation sequencing (NGS) [24]; however, their sensitivities and accuracies are different. Furthermore, turn-around time, an obstacle in deciding the treatment, varies according to the test. As NGS usually takes 2–4 weeks to generate mutation data, it is critical to obtain rapid results using FLT3 PCR tests when treatment decisions need to be made quickly. In addition, to determine prognosis at diagnosis, it is necessary to conduct a quantitative analysis of FLT3-ITD [4]. In the 2017 ELN risk stratification model, the presence of FLT3-ITD mutations is classified according to allelic ratio [4]. The allelic ratio is calculated as the ratio of the area under the curve of the mutant allele to the wild-type allele. However, NGS can quantify FLT3-ITD results in variant allele frequency (VAF). VAF is calculated as the fraction of mutant alleles as a percentage of all FLT3 alleles (wild-type+mutant). Therefore, there is a need for caution in the interpretation of the FLT3-ITD mutant burden based on the VAF and allelic ratio.


The prognostic impact of FLT3-ITD in AML is affected by the mutant allelic ratio and co-mutation status of nucleophosmin 1 (NPM1) [4]. The 2017 ELN guidelines stratify FLT3-ITD AML into three risk groups: 1) AML with an FLT3-ITD high allelic ratio (>0.5) in the absence of NPM1 mutations is stratified as an adverse risk category; 2) FLT3-ITD low allelic ratio (≤0.5) is associated with favorable risk in patients with NPM1 co-mutation; and 3) intermediate risk is observed in patients with NPM1 wild-type and FLT3-ITD low allelic ratio or NPM1 mutated and FLT3-ITD high allelic ratio [4, 25]. However, a study on patients with intermediate cytogenetic risk showed a high relapse rate (68–79%) regardless of the allelic burden of FLT3-ITD in patients with NPM1 and FLT3-ITD mutated AML [26]. Oran et al. [27] also reported that allogeneic hematopoietic cell transplantation (HCT) improves relapse-free survival (RFS) and OS compared with those with consolidation chemotherapy, regardless of the allelic ratio in FLT3-ITD mutated AML. An FLT3-ITD low allelic ratio is not as favorable as the FLT3-ITD wild-type in patients with AML and NPM1 mutations, as seen previously. Allogeneic HCT for post-remission therapy may be considered to reduce the relapse risk even in patients with FLT3-ITD low allelic ratio, regardless of NPM1 mutation status [12, 26-28].

The prognostic relevance of FLT3-TKD mutations is conflicting [29]. However, the importance of FLT3-TKD mutations is emerging as targetable FLT3 inhibitors have been introduced [7, 23, 30].


FLT3 tyrosine kinase inhibitors differ in potency, selectivity, mode of binding, and protein binding [31]. Type I FLT3 inhibitors bind in the kinase-active conformation, whereas type II inhibitors bind in the inactive conformation [24]. Representative type I inhibitors include midostaurin, gilteritinib, and crenolanib, whereas type II inhibitors include quizartinib and sorafenib. In general, type II FLT3 inhibitors have increased selectivity compared with that for type I FLT3 inhibitors (Table 1) [32].

Table 1

Summary of clinically applicable FLT3 inhibitors for FLT3-mutated AML.

Patient eligibilityDisease statusDrugTarget mutated lesionRepresentative trialUsageBenefitApprovalIn Korea
Intensive induction eligibleNewly diagnosedMidostaurinFLT3-ITD/TKDRATIFY (Phase3) [7]Combination with 7+3 induction and consolidation chemotherapyMedian OS (74.7 vs. 25.6 mo), P=0.009FDA, EMAAvailable
MaintenanceMidostaurinFLT3-ITD/TKDRATIFY (Phase3) [7]Maintain until relapse for up to 12 monthsas the extension of RATIFY trialEMANot available
Post-HCT maintenanceSorafenibFLT3-ITDSORMAIN (Phase 2) [9]Maintain untilrelapse for up to 24 months2-year RFS (85 vs. 53%), P=0.002Off-labelNot available
Relapsed or refractoryGilteritinibFLT3-ITD/TKDADMIRAL (Phase 3)MonotherapyMedian OS (9.3 vs. 5.6 mo), P<0.001FDA, EMAAvailable
Intensive induction ineligibleNewly diagnosedSorafenibFLT3-ITDNCT02196857 (Phase 2) and NCT01254890 Phase 1/2) [35]Combination with azacitidineMedian OS (8.3 mo)Off-labelNot available
Relapsed or refractorySorafenibFLT3-ITDNCT01254890 [36]Combination with azacitidineResponse rate: 46%Off-labelNot available

Abbreviations: AML, acute myeloid leukemia; EMA, European Medicines Agency; FDA, Food and Drug Administration; FLT3, FMS-like tyrosine kinase 3; HCT, hematopoietic cell transplantation; ITD, internal tandem duplication; mo, months; OS, overall survival; RFS, relapse-free survival; TKD, tyrosine kinase domain.


Midostaurin was one of the first FLT3 inhibitors to be studied in patients with AML. In the phase 3 RATIFY trial, midostaurin was evaluated in combination with standard induction and consolidation therapy and maintenance in young adults (<60 yr) with newly diagnosed FLT3-mutated AML [7]. This regimen was used for FLT3-ITD- and TKD-mutated AML. The combination of midostaurin with standard 7+3 induction chemotherapy has been shown to improve OS significantly, with a median OS of 74.7 months in patients receiving midostaurin plus chemotherapy vs. 25.6 months in patients receiving 7+3 chemotherapy alone (hazard ratio=0.78, P=0.009). Based on the results of this study, midostaurin was approved for clinical use by the U.S. Food and Drug Administration (FDA) in April 2017. The RATIFY trial was designed for maintenance with midostaurin for 12 months in young patients (18–60 yr). Older patients (≥60 yr) were not enrolled in the RATIFY trial; however, no age restrictions were imposed for midostaurin combination therapy in the FDA approval. A phase 2 trial was extended to patients up to 70 years of age for midostaurin plus intensive chemotherapy [33]. Compared with that for historical controls, midostaurin significantly improved event-free survival in overall age (hazard ratio=0.58, 95% CI, 0.48–0.70) and in older patients (hazard ratio=0.42, 95% CI, 0.29–0.61). However, the FDA has not approved midostaurin for maintenance therapy after consolidation or allogeneic transplantation. The European Medicines Agency (EMA) granted marketing authorization for midostaurin in 2017. The EMA included an indication for midostaurin maintenance therapy until relapse for up to 12 months in adult patients in complete remission following induction and consolidation.


Gilteritinib is a potent type I FLT3 inhibitor that targets FLT3-ITD and FLT3-TKD mutations. The FDA and EMA approved gilteritinib monotherapy for relapsed or refractory (R/R) FLT3-mutated AML based on the interim data of the Phase 3 ADMIRAL trial [23]. The ADMIRAL trial evaluated gilteritinib monotherapy vs. investigator-choice salvage chemotherapy in patients with R/R FLT3-mutated AML. Compared with that for salvage chemotherapy, gilteritinib showed significantly superior complete remission (CR) and CR with hematologic improvement (CRh) rate (34% vs. 15%, P=0.0001) and decreased the death rate by 36%, with a median OS of 9.3 months vs. 5.6 months (P<0.001).

A phase 3 trial is ongoing to determine whether gilteritinib has therapeutic benefits similar to those of midostaurin in newly diagnosed AML with FLT3 mutations (NCT04027309, HOVON 156 AML trial). The HOVON 156 AML trial compared gilteritinib with midostaurin combined with intensive chemotherapy, followed by maintenance therapy. Additionally, an ongoing phase 3 trial is being conducted to elucidate the role of gilteritinib in post-transplant maintenance (NCT 02997202, MORPHO trial) and following induction/consolidation therapy (NCT02927262) in patients with FLT3- ITD-mutated AML.


Quizartinib is a second-generation potent type II FLT3 inhibitor. A phase 3 randomized controlled trial (QuANTUM-R) evaluated quizartinib monotherapy vs. investigator choice salvage chemotherapy in patients with R/R FLT3-ITD-mutated AML [8]. OS was longer in the quizartinib group than that in the chemotherapy group [hazard ratio 0.76 (95% CI, 0.58–0.98; P=0.02)]. The median OS was 6.2 months (5.3–7.2) in the quizartinib group and 4.7 months (4.0–5.5) in the chemotherapy group, and 32% of the patients in the quizartinib group underwent allogeneic transplantation compared with 11% of the patients in the salvage chemotherapy group. Despite these positive results, both the FDA and EMA have rejected the marketing authorization for quizartinib because of various reasons, such as dropouts (23% of the control group did not receive chemotherapy) and concerns about cardiac and infection adverse events. However, Japan has approved quizartinib as a monotherapy for R/R FLT3-ITD-mutated AML. In patients with newly diagnosed AML, quizartinib is currently being evaluated in the Phase 3 QuANTUM-First trial, which compares quizartinib vs. placebo with 7+3 induction, consolidation, and maintenance (NCT02668653). Owing to improved efficacy and selectivity, the second-generation type II FLT3 inhibitor quizartinib achieved much higher single-agent clinical response rates than those with the first-generation type I FLT3 inhibitor midostaurin. Despite the high response rates achieved with quizartinib in patients with R/R FLT3-ITD-mutated AML, the responses were not strong. Most patients relapsed because of secondary FLT3-TKD mutations, impairing quizartinib binding [34].


Sorafenib is a first-generation, type II FLT3 inhibitor. It remains unapproved for use in patients with AML; however, several studies have shown its potential in FLT3-ITD-mutated AML. A phase 2, randomized, placebo-controlled trial (SORAML) evaluated 7+3 induction and consolidation with or without sorafenib in young individuals (<60 yr) with newly diagnosed AML, regardless of FLT3-ITD mutation status. Sorafenib improved event-free survival (21 mo vs. 9 mo, P=0.013) but not OS. Sorafenib with azacitidine, as a front-line strategy in older patients (≥60 yr) with FLT3- ITD-mutated AML who could not tolerate intensive induction, reported an overall response rate of 78% [CR: 26%, CR with incomplete count recovery (CRi)/CR with incomplete platelet recovery (CRp): 44%, and partial response (PR): 7%] [35]. Sorafenib combined with azacitidine demonstrated an overall response rate of 46% (CR: 16%, CRi: 27%, PR: 3%) for FLT3-ITD-mutated R/R AML [36].

The SORMAIN trial (a placebo-controlled, randomized, phase 2 trial) evaluated sorafenib maintenance therapy in patients with FLT3-ITD-mutated AML undergoing allogeneic HCT. The hazard ratio (HR) for relapse or death for sorafenib vs. placebo was 0.39 (95% CI, 0.18–0.85; log-rank P=0.013). The probability of 24-month RFS was 85.0% (95% CI, 0.70–0.93) with sorafenib (HR, 0.256; 95% CI, 0.10–0.65) and 53.3% (95% CI, 0.36–0.68) with placebo (log-rank P=0.002) [9]. In another phase 3 trial, sorafenib also demonstrated a decreased 1-year cumulative incidence of relapse (7.0% vs. 24.5%, P=0.001) and improved OS (82.1% vs. 68%, P=0.012) without treatment-related deaths [11]. The post-transplant maintenance results for sorafenib suggest potential synergy with post-transplant alloimmune effects [12, 37].


Rapid determination of FLT3 mutations during diagnosis or relapse is essential for making treatment decisions to manage AML and for the early selection of FLT3-targeting agents. The current standard treatment for a patient with a newly diagnosed FLT3-mutated AML is 7+3 induction chemotherapy combined with midostaurin [10]. In FLT3-mutated AML, allogeneic HCT as a post-remission therapy is considered to lower the risk of relapse. Although the role of post-transplant maintenance with FLT3 inhibitors has not been established, experts recommend maintenance therapy to reduce relapse risk [10, 12]. Gilteritinib is more effective than salvage chemotherapy for R/R FLT3-mutated AML. Ongoing trials are expected to provide additional treatment options depending on the disease state and patient vulnerability to FLT3-mutated AML.

Authors’ Disclosures of Potential Conflicts of Interest

No potential conflicts of interest relevant to this article were reported.

  1. Park EH, Lee H, Won YJ, et al. Nationwide statistical analysis of myeloid malignancies in Korea: incidence and survival rate from 1999 to 2012. Blood Res 2015;50:204-17.
    Pubmed PMC CrossRef
  2. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209-21.
    Pubmed PMC CrossRef
  3. Ahn JS, Kim HJ, Kim YK, et al. Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype. Oncotarget 2018;9:4961-8.
    Pubmed PMC CrossRef
  4. D?hner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129:424-47.
    Pubmed PMC CrossRef
  5. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 1996;10:1911-8.
  6. D?hner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 2005;106:3740-6.
    Pubmed CrossRef
  7. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 2017;377:454-64.
    Pubmed PMC CrossRef
  8. Cortes JE, Khaled S, Martinelli G, et al. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2019;20:984-97.
    Pubmed CrossRef
  9. 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;38:2993-3002.
    Pubmed CrossRef
  10. Tallman MS, Wang ES, Altman JK, et al. Acute myeloid leukemia, version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019;17:721-49.
    Pubmed CrossRef
  11. Xuan L, Wang Y, Huang F, et al. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol 2020;21:1201-12.
    Pubmed CrossRef
  12. Daver N, Venugopal S, Ravandi F. FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm. Blood Cancer J 2021;11:104.
    Pubmed PMC CrossRef
  13. Lyman SD, Williams DE. Biology and potential clinical applications of flt3 ligand. Curr Opin Hematol 1995;2:177-81.
    Pubmed CrossRef
  14. Gotze KS, Ramirez M, Tabor K, Small D, Matthews W, Civin CI. Flt3high and Flt3low CD34+ progenitor cells isolated from human bone marrow are functionally distinct. Blood 1998;91:1947-58.
    Pubmed CrossRef
  15. Schnittger S, Bacher U, Haferlach C, Alpermann T, Kern W, Haferlach T. Diversity of the juxtamembrane and TKD1 mutations (exons 13-15) in the FLT3 gene with regards to mutant load, sequence, length, localization, and correlation with biological data. Genes Chromosomes Cancer 2012;51:910-24.
    Pubmed CrossRef
  16. Naoe T, Kiyoe H, Yamamoto Y, et al. FLT3 tyrosine kinase as a target molecule for selective antileukemia therapy. Cancer Chemother Pharmacol 2001;48(Suppl 1):S27-30.
    Pubmed CrossRef
  17. Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 2000;19:624-31.
    Pubmed CrossRef
  18. Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001;97:2434-9.
    Pubmed CrossRef
  19. Janke H, Pastore F, Schumacher D, et al. Activating FLT3 mutants show distinct gain-of-function phenotypes in vitro and a characteristic signaling pathway profile associated with prognosis in acute myeloid leukemia. PLoS One 2014;9:e89560.
    Pubmed PMC CrossRef
  20. Choudhary C, Schw?ble J, Brandts C, et al. AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood 2005;106:265-73.
    Pubmed CrossRef
  21. Shih LY, Huang CF, Wu JH, et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood 2002;100:2387-92.
    Pubmed CrossRef
  22. Schmalbrock LK, Dolnik A, Cocciardi S, et al. Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin. Blood 2021;137:3093-104.
    Pubmed PMC CrossRef
  23. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med 2019;381:1728-40.
    Pubmed CrossRef
  24. Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia 2019;33:299-312.
    Pubmed PMC CrossRef
  25. Pratcorona M, Brunet S, Nomded?u J, et al. 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 2013;121:2734-8.
    Pubmed CrossRef
  26. Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE. Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood 2014;124:273-6.
    Pubmed CrossRef
  27. Oran B, Cortes J, Beitinjaneh A, et al. Allogeneic transplantation in first remission improves outcomes irrespective of FLT3-ITD allelic ratio in FLT3-ITD-positive acute myelogenous leukemia. Biol Blood Marrow Transplant 2016;22:1218-26.
    Pubmed PMC CrossRef
  28. Sakaguchi M, Yamaguchi H, Najima Y, et al. Prognostic impact of low allelic ratio FLT3- ITD and NPM1 mutation in acute myeloid leukemia. Blood Adv 2018;2:2744-54.
    Pubmed PMC CrossRef
  29. Mead AJ, Linch DC, Hills RK, Wheatley K, Burnett AK, Gale RE. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood 2007;110:1262-70.
    Pubmed CrossRef
  30. 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 2008;111:2527-37.
    Pubmed CrossRef
  31. Smith CC. FLT3 inhibition in acute myeloid leukemia. Clin Lymphoma Myeloma Leuk 2020;20(Suppl 1):S5-6.
    Pubmed CrossRef
  32. Sexauer AN, Tasian SK. Targeting FLT3 signaling in childhood acute myeloid leukemia. Front Pediatr 2017;5:248.
    Pubmed PMC CrossRef
  33. Schlenk RF, Weber D, Fiedler W, et al. Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood 2019;133:840-51.
    Pubmed CrossRef
  34. Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012;485:260-3.
    Pubmed PMC CrossRef
  35. Ohanian M, Garcia-Manero G, Levis M, et al. Sorafenib combined with 5-azacytidine in older patients with untreated FLT3-ITD mutated acute myeloid leukemia. Am J Hematol 2018;93:1136-41.
    Pubmed CrossRef
  36. 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;121:4655-62.
    Pubmed PMC CrossRef
  37. Metzelder SK, Schroeder T, Finck A, et al. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia 2012;26:2353-9.
    Pubmed CrossRef


This Article

Current Issue


SCImago Journal & Country Rank

Indexed/Covered by

Today : 203  /
Total : 458,272