A new FLT3 inhibitor with two cases: the gilteritinib experience

被引:0
作者
Serin, Istemi [1 ]
Dogu, Mehmet Hilmi [2 ]
Huq, Gulben Erdem [3 ]
Yokus, Osman [1 ]
机构
[1] Univ Hlth Sci, Istanbul Training & Res Hosp, Dept Hematol Istanbul, Istanbul, Turkey
[2] Istinye Univ, Liv Hosp Ulus, Dept Internal Med & Hematol, Istanbul, Turkey
[3] Univ Hlth Sci, Istanbul Training & Res Hosp, Dept Pathol Istanbul, Istanbul, Turkey
关键词
Acute myeloid leukemia; refractory; FLT3; gilteritinib; prognosis; ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; RESISTANCE; MUTATIONS; CHEMOTHERAPY; ACTIVATION; GENE;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Introduction: In acute myeloid leukemia (AML), a heterogeneous group of leukemias, there are various factors to determine prognosis. Among these prognostic factors, cytogenetic results are increasing in importance day by day. FLT3 mutations are among the most common molecular abnormalities in AML, patients with recurrent or refractory (R/R) AML with this mutation have a low response rate to salvage therapy. Gilteritinib has activity against FLT3, ALK and AXL. This article shall present two cases, for which Gilteritinib was used, a new FLT3 inhibitor, and the results of the treatment. Case 1: A 52-year-old female patient presented to the emergency clinic with weakness and fever. In initial biochemical analysis, leukocyte was 104000/mm(3). Peripheral smear contained diffuse myeloid blastoid cells, peripheral blood flow cytometry also supported the AML M0-1 phenotype. The bone marrow biopsy aspiration performed on the 14th day of induction "3+7" treatment, contained diffuse blastic infiltrate and supported refractory disease. In addition to the FLAG-IDA salvage regimen, 120 mg/day Gilteritinib was also started. Bone marrow aspiration performed on the 28th day of salvage therapy was compatible with remission. Case 2: 53 years old male patient with also no comorbidity other than known hypertension. In the initial biochemical analysis of the patient, leukocyte was 156000/mm(3), platelet 58000/mm(3) and hemoglobin 7.6 g/dl. Peripheral blood flow cytometry supported the AML M5 phenotype, whose peripheral smear showed diffuse monoblastoid cells. On the 14th day of the patient's 3+7 induction treatment, the control bone marrow aspiration showed diffuse blast infiltration and was considered refractory, FLAG-IDA salvage therapy with again 120 mg/day Gilteritinib per oral were started. On the 28th day, control bone marrow aspiration was evaluated as remission. Discussion and conclusion: Unlike other FLT 3 inhibitors, Gilteritinib has been shown to be a highly effective agent in R/R AML with FLT3 mutations. Being the first data to be reported from Turkey, we think it would be quite guiding the titular.
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页码:271 / 278
页数:8
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共 30 条
[1]   Durable remission of post-transplant relapsed FLT3-ITD AML in response to gilteritinib administration after a second transplant from the same donor [J].
Ando, Toshihiko ;
Sano, Haruna ;
Yokoo, Masako ;
Kusaba, Kana ;
Kidoguchi, Keisuke ;
Yamaguchi, Kyosuke ;
Katsuya, Hiroo ;
Yoshihara, Satoshi ;
Kubota, Yasushi ;
Kojima, Kensuke ;
Kimura, Shinya .
INTERNATIONAL JOURNAL OF HEMATOLOGY, 2020, 112 (02) :249-253
[2]   Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial [J].
Cortes, Jorge ;
Perl, Alexander E. ;
Dohner, Hartmut ;
Kantarjian, Hagop ;
Martinelli, Giovanni ;
Kovacsovics, Tibor ;
Rousselot, Philippe ;
Steffen, Bjorn ;
Dombret, Herve ;
Estey, Elihu ;
Strickland, Stephen ;
Altman, Jessica K. ;
Baldus, Claudia D. ;
Burnett, Alan ;
Kramer, Alwin ;
Russell, Nigel ;
Shah, Neil P. ;
Smith, Catherine C. ;
Wang, Eunice S. ;
Ifrah, Norbert ;
Gammon, Guy ;
Trone, Denise ;
Lazzaretto, Deborah ;
Levis, Mark .
LANCET ONCOLOGY, 2018, 19 (07) :889-903
[3]   Secondary mutations as mediators of resistance to targeted therapy in leukemia [J].
Daver, Naval ;
Cortes, Jorge ;
Ravandi, Farhad ;
Patel, Keyur P. ;
Burger, Jan A. ;
Konopleva, Marina ;
Kantarjian, Hagop .
BLOOD, 2015, 125 (21) :3236-3245
[4]   How I treat acute myeloid leukemia in the era of new drugs [J].
DiNardo, Courtney D. ;
Wei, Andrew H. .
BLOOD, 2020, 135 (02) :85-96
[5]   Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].
Doehner, Hartmut ;
Estey, Elihu ;
Grimwade, David ;
Amadori, Sergio ;
Appelbaum, Frederick R. ;
Buechner, Thomas ;
Dombret, Herve ;
Ebert, Benjamin L. ;
Fenaux, Pierre ;
Larson, Richard A. ;
Levine, Ross L. ;
Lo-Coco, Francesco ;
Naoe, Tomoki ;
Niederwieser, Dietger ;
Ossenkoppele, Gert J. ;
Sanz, Miguel ;
Sierra, Jorge ;
Tallman, Martin S. ;
Tien, Hwei-Fang ;
Wei, Andrew H. ;
Lowenberg, Bob ;
Bloomfield, Clara D. .
BLOOD, 2017, 129 (04) :424-447
[6]   Phase IIB Trial of Oral Midostaurin (PKC412), the FMS-Like Tyrosine Kinase 3 Receptor (FLT3) and Multi-Targeted Kinase Inhibitor, in Patients With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome With Either Wild-Type or Mutated FLT3 [J].
Fischer, Thomas ;
Stone, Richard M. ;
DeAngelo, Daniel J. ;
Galinsky, Ilene ;
Estey, Elihu ;
Lanza, Carlo ;
Fox, Edward ;
Ehninger, Gerhard ;
Feldman, Eric J. ;
Schiller, Gary J. ;
Klimek, Virginia M. ;
Nimer, Stephen D. ;
Gilliland, D. Gary ;
Dutreix, Catherine ;
Huntsman-Labed, Alice ;
Virkus, Jodi ;
Giles, Francis J. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (28) :4339-4345
[7]   Targeting AML-associated FLT3 mutations with a type I kinase inhibitor [J].
Jones, LaQuita M. ;
Melgar, Katelyn ;
Bolanos, Lyndsey ;
Hueneman, Kathleen ;
Walker, Morgan M. ;
Jiang, Jian-Kang ;
Wilson, Kelli M. ;
Zhang, Xiaohu ;
Shen, Jian ;
Jiang, Fan ;
Sutter, Patrick ;
Wang, Amy ;
Xu, Xin ;
Tawa, Gregory J. ;
Hoyt, Scott B. ;
Wunderlich, Mark ;
O'Brien, Eric ;
Perentesis, John P. ;
Starczynowski, Daniel T. ;
Thomas, Craig J. .
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (04) :2017-2023
[8]   Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation [J].
Kamitani, Iku ;
Saito, Takeshi ;
Yokoyama, Hiroki ;
Nakano, Aya ;
Ishii, Hiroto ;
Tanoue, Susumu ;
Hattori, Daiki ;
Oshima, Sayaka ;
Ishii, Shoko ;
Gunji, Tadahiro ;
Fukushima, Ryoko ;
Katsube, Atsushi ;
Shimada, Takaki ;
Nishiwaki, Kaichi ;
Dobashi, Nobuaki ;
Yano, Shingo .
JOURNAL OF INFECTION AND CHEMOTHERAPY, 2021, 27 (04) :639-641
[9]   Successful treatment with gilteritinib for isolated extramedullary relapse of acute myeloid leukemia with FLT3-ITD mutation after allogeneic stem cell transplantation [J].
Kida, Michiko ;
Kuroda, Yoshiaki ;
Kido, Miki ;
Chishaki, Ren ;
Kuraoka, Kazuya ;
Ito, Takuo .
INTERNATIONAL JOURNAL OF HEMATOLOGY, 2020, 112 (02) :243-248
[10]   Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product [J].
Kiyoi, H ;
Towatari, M ;
Yokota, S ;
Hamaguchi, M ;
Ohno, R ;
Saito, H ;
Naoe, T .
LEUKEMIA, 1998, 12 (09) :1333-1337