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OncoTargets and Therapy Volume 15, 2022 - Issue
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Case Series

Rapid and Efficient Response to Gilteritinib and Venetoclax-Based Therapy in Two AML Patients with FLT3-ITD Mutation Unresponsive to Venetoclax Plus Azacitidine

Lei-Si Zhang1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Jun Wang1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Ming-Zhu Xu1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Tian-Mei Wu1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Si-Man Huang1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaORCID Iconhttps://orcid.org/0000-0002-2131-6608View further author information
ORCID Icon,
Han-Yu Cao1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaView further author information
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Ai-Ning Sun1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaView further author information
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Song-Bai Liu3 Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, People’s Republic of ChinaCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-3920-1032View further author information
ORCID Icon &
Sheng-Li Xue1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China;2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0003-4609-616XView further author information
ORCID Icon show all
Pages 159-164 | Published online: 18 Feb 2022

References

  • Aldoss I, Zhang J, Mei M, et al. Venetoclax and hypomethylating agents in FLT3‐mutated acute myeloid leukemia. Am J Hematol. 2020;95(10):1193–1199. doi:10.1002/ajh.25929
  • Smith CC, Wang Q, Chin C, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012;485(7397):260–263. doi:10.1038/nature11016
  • Xu F, Han R, Zhang J, et al. The role of FLT3-ITD mutation on de Novo MDS in Chinese population. Clin Lymphoma Myeloma Leuk. 2019;19(2):e107–15. doi:10.1016/j.clml.2018.11.006
  • DiNardo CD, Rausch CR, 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;93(3):401–407. doi:10.1002/ajh.25000
  • Chyla B, Daver N, Doyle K, et al. Genetic biomarkers of sensitivity and resistance to venetoclax monotherapy in patients with relapsed acute myeloid leukemia. Am J Hematol. 2018;93(8):E202–5. doi:10.1002/ajh.25146
  • Ramsey HE, Fischer MA, Lee T, et al. A novel MCL1 inhibitor combined with venetoclax rescues venetoclax-resistant acute myelogenous leukemia. Cancer Discov. 2018;8(12):1566–1581. doi:10.1158/2159-8290.CD-18-0140
  • Bagrintseva K, Geisenhof S, Kern R, et al. FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L). Blood. 2005;105(9):3679–3685. doi:10.1182/blood-2004-06-2459
  • Singh MR, Zhang Q, DeFilippis RA, et al. Venetoclax combines synergistically with FLT3 inhibition to effectively target leukemic cells in FLT3-ITD+ acute myeloid leukemia models. Haematologica. 2021;106(4):1034–1046. doi:10.3324/haematol.2019.244020
  • Ma J, Zhao S, Qiao X, et al. Inhibition of Bcl-2 synergistically enhances the antileukemic activity of midostaurin and gilteritinib in preclinical models of FLT3-mutated acute myeloid leukemia. Clin Cancer Res. 2019;25(22):6815–6826. doi:10.1158/1078-0432.CCR-19-0832
  • Pulte ED, Norsworthy KJ, Wang Y, et al. FDA approval summary: gilteritinib for relapsed or refractory acute myeloid leukemia with a FLT3 mutation. Clin Cancer Res. 2021;27(13):3515–3521. doi:10.1158/1078-0432.CCR-20-4271
  • Altman JK, Perl AE, Hill JE, Rosales M, Bahceci E, Levis MJ. The impact of FLT3 mutation clearance and treatment response after gilteritinib therapy on overall survival in patients with FLT3 mutation–positive relapsed/refractory acute myeloid leukemia. Cancer Med. 2021;10(3):797–805. doi:10.1002/cam4.3652
  • Maiti A, Rausch CR, Cortes JE, et al. Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens. Haematologica. 2021;106(3):894–898. doi:10.3324/haematol.2020.252569
  • Esteve J, Schots R, Bernal T, et al. Multicenter, open-label, 3-arm study of gilteritinib, gilteritinib plus azacitidine, or azacitidine alone in newly diagnosed FLT3 mutated (FLT3mut+) acute myeloid leukemia (AML) patients ineligible for intensive induction chemotherapy: findings from the safety Cohort. Blood. 2018;132:2736.

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