FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation

被引：6

作者：

Blackmon, Amanda ^{[1
]}

Aldoss, Ibrahim ^{[1
]}

Ball, Brian J. ^{[1
,2
]}

机构：

[1] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Dept Hematol & HCT, Div Leukemia, 1500 E Duarte Rd, Duarte, CA 91010 USA

来源：

BLOOD AND LYMPHATIC CANCER-TARGETS AND THERAPY | 2022年 / 12卷

关键词：

FLT3; inhibitor; posttransplantation; maintenance; stem -cell transplantation; midostaurin; sorafenib; ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; MINIMAL RESIDUAL DISEASE; TYROSINE KINASE INHIBITORS; ACUTE MYELOGENOUS LEUKEMIA; PHASE-I; PROGNOSTIC-SIGNIFICANCE; SORAFENIB MAINTENANCE; ALLELIC RATIO; AML;

D O I：

10.2147/BLCTT.S281252

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutations in the FLT3 gene are associated with poor prognosis in patients with AML, even after consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in first remission. Treatment failure in FLT3-mutated AML is largely driven by excessive risk of relapse compared to other genetic subtypes, including in patients post-alloHCT. As a result, there is substantial interest in studying posttransplant maintenance therapy in FLT3-mutated AML as an approach to optimize disease control and improve long-term outcomes. Clinical trials utilizing posttransplant FLT3 inhibitors, such as sorafenib and midostaurin, have shown feasibility, safety, and encouraging posttransplant outcomes, and there are ongoing studies using newer-generation tyrosine-kinase inhibitors as posttransplant maintenance therapy. Here, we review the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlight key remaining questions.

引用

页码：137 / 147

页数：11

共 74 条

[51] A Prospective Study of Peritransplant Sorafenib for Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Transplantation [J].

Pratz, Keith W. ;

Rudek, Michelle A. ;

Smith, B. Douglas ;

Karp, Judith ;

Gojo, Ivana ;

Dezern, Amy ;

Jones, Richard J. ;

Greer, Jackie ;

Gocke, Christopher ;

Baer, Maria R. ;

Duong, Vu H. ;

Rosner, Gary ;

Zahurak, Marianna ;

Wright, John J. ;

Emadi, Ashkan ;

Levis, Mark .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2020, 26 (02) :300-306

[52] How I treat FLT3-mutated AML [J].

Pratz, Keith W. ;

Levis, Mark .

BLOOD, 2017, 129 (05) :565-571

[53] Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C [J].

Propper, DJ ;

McDonald, AC ;

Man, A ;

Thavasu, P ;

Balkwill, F ;

Braybrooke, JP ;

Caponigro, F ;

Graf, P ;

Dutreix, C ;

Blackie, R ;

Kaye, SB ;

Ganesan, TS ;

Talbot, DC ;

Harris, AL ;

Twelves, C .

JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (05) :1485-1492

[54] Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia [J].

Ravandi, Farhad ;

Jorgensen, Jeffrey ;

Borthakur, Gautam ;

Jabbour, Elias ;

Kadia, Tapan ;

Pierce, Sherry ;

Brandt, Mark ;

Wang, Sa ;

Konoplev, Sergej ;

Wang, Xuemei ;

Huang, Xuelin ;

Daver, Naval ;

DiNardo, Courtney ;

Andreeff, Michael ;

Konopleva, Marina ;

Estrov, Zeev ;

Garcia-Manero, Guillermo ;

Cortes, Jorge ;

Kantarjian, Hagop .

CANCER, 2017, 123 (03) :426-435

[55] Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial [J].

Rollig, Christoph ;

Serve, Hubert ;

Huettmann, Andreas ;

Noppeney, Richard ;

Mueller-Tidow, Carsten ;

Krug, Utz ;

Baldus, Claudia D. ;

Brandts, Christian H. ;

Kunzmann, Volker ;

Einsele, Hermann ;

Kraemer, Alwin ;

Schaefer-Eckart, Kerstin ;

Neubauer, Andreas ;

Burchert, Andreas ;

Giagounidis, Aristoteles ;

Krause, Stefan W. ;

Mackensen, Andreas ;

Aulitzky, Walter ;

Herbst, Regina ;

Haenel, Mathias ;

Kiani, Alexander ;

Frickhofen, Norbert ;

Kullmer, Johannes ;

Kaiser, Ufrich ;

Link, Hartmut ;

Geer, Thomas ;

Reiche, Albert ;

Junghanss, Christian ;

Repp, Roland ;

Heits, Frank ;

Duerk, Heinz ;

Hase, Jana ;

Klut, Ina-Maria ;

Illmer, Thomas ;

Bornhaeuser, Martin ;

Schaich, Markus ;

Parmentier, Stefani ;

Goerner, Martin ;

Thiede, Christian ;

von Bonin, Malte ;

Schetelig, Johannes ;

Kramer, Michael ;

Berdel, Welfgang E. ;

Ehninger, Gerhard .

LANCET ONCOLOGY, 2015, 16 (16) :1691-1699

[56]

Rosnet O, 1996, ACTA HAEMATOL-BASEL, V95, P218

[57] Allogeneic Hematopoietic Stem Cell Transplantation in FLT3-ITD-Positive Acute Myelogenous Leukemia: The Role for FLT3 Tyrosine Kinase Inhibitors Post-Transplantation [J].

Schiller, Gary J. ;

Tuttle, Pamela ;

Desai, Pinkal .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2016, 22 (06) :982-990

[58] Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia [J].

Schlenk, Richard F. ;

Doehner, Konstanze ;

Krauter, Juergen ;

Froehling, Stefan ;

Corbacioglu, Andrea ;

Bullinger, Lars ;

Habdank, Marianne ;

Spaeth, Daniela ;

Morgan, Michael ;

Benner, Axel ;

Schlegelberger, Brigitte ;

Heil, Gerhard ;

Ganser, Arnold ;

Doehner, Hartmut .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (18) :1909-1918

[59] Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD [J].

Schlenk, Richard F. ;

Weber, Daniela ;

Fiedler, Walter ;

Salih, Helmut R. ;

Wulf, Gerald ;

Salwender, Hans ;

Schroeder, Thomas ;

Kindler, Thomas ;

Luebber, Michael ;

Wolf, Dominik ;

Westermann, Joerg ;

Kraemer, Doris ;

Goetze, Katharina S. ;

Horst, Heinz-August ;

Krauter, Juergen ;

Girschikofsky, Michael ;

Ringhoffer, Mark ;

Suedhoff, Thomas ;

Held, Gerhard ;

Derigs, Hans-Guenter ;

Schroers, Roland ;

Greil, Richard ;

Griesshammer, Martin ;

Lange, Elisabeth ;

Burchardt, Alexander ;

Martens, Uwe ;

Hertenstein, Bernd ;

Marretta, Lore ;

Heuser, Michael ;

Thol, Felicitas ;

Gaidzik, Verena, I ;

Herr, Wolfgang ;

Krzykalla, Julia ;

Benner, Axel ;

Doehner, Konstanze ;

Ganser, Arnold ;

Paschka, Peter ;

Doehner, Hartmut .

BLOOD, 2019, 133 (08) :840-851

[60] Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation [J].

Schlenk, Richard F. ;

Kayser, Sabine ;

Bullinger, Lars ;

Kobbe, Guido ;

Casper, Jochen ;

Ringhoffer, Mark ;

Held, Gerhard ;

Brossart, Peter ;

Luebbert, Michael ;

Salih, Helmut R. ;

Kindler, Thomas ;

Horst, Heinz A. ;

Wulf, Gerald ;

Nachbaur, David ;

Goetze, Katharina ;

Lamparter, Alexander ;

Paschka, Peter ;

Gaidzik, Verena I. ;

Teleanu, Veronica ;

Spaeth, Daniela ;

Benner, Axel ;

Krauter, Juergen ;

Ganser, Arnold ;

Doehner, Hartmut ;

Doehner, Konstanze .

BLOOD, 2014, 124 (23) :3441-3449

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