Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO

被引：17

作者：

Dumas, Pierre-Yves ^{[1
]}

Raffoux, Emmanuel ^{[2
]}

Berard, Emilie ^{[3
]}

Bertoli, Sarah ^{[4
]}

Hospital, Marie-Anne ^{[5
]}

Heiblig, Mael ^{[6
]}

Desbrosses, Yohann ^{[7
]}

Bonmati, Caroline ^{[8
]}

Pautas, Cecile ^{[9
]}

Lambert, Juliette ^{[10
]}

Orvain, Corentin ^{[11
,12
]}

Banos, Anne ^{[13
]}

Pasquier, Florence ^{[14
]}

Peterlin, Pierre ^{[15
]}

Marchand, Tony ^{[16
]}

Uzunov, Madalina ^{[17
]}

Frayfer, Jamile ^{[18
]}

Turlure, Pascal ^{[19
]}

Cluzeau, Thomas ^{[20
]}

Jourdan, Eric ^{[21
]}

Himberlin, Chantal ^{[22
]}

Tavernier, Emmanuelle ^{[23
]}

Villate, Alban ^{[24
]}

Haiat, Stephanie ^{[25
]}

Chretien, Marie-Lorraine ^{[26
]}

Carre, Martin ^{[27
]}

Chantepie, Sylvain ^{[28
]}

Vaida, Ioana ^{[29
]}

Wemeau, Mathieu ^{[30
]}

Chebrek, Safia ^{[31
]}

Guillerm, Gaelle ^{[32
]}

Guieze, Romain ^{[33
,34
]}

Debarri, Houria ^{[35
]}

Gehlkopf, Eve ^{[36
]}

Laribi, Kamel ^{[37
]}

Marcais, Ambroise ^{[38
]}

Santagostino, Alberto ^{[39
]}

Bene, Marie-Christine ^{[40
]}

Mineur, Ariane ^{[1
]}

Pigneux, Arnaud ^{[1
]}

Dombret, Herve ^{[2
]}

Recher, Christian ^{[4
]}

机构：

[1] CHU Bordeaux, Serv Hematol Clin & Therapie Cellulaire, F-33000 Bordeaux, France

[2] Hop St Louis, AP HP, Serv Hematol Adultes, Paris, France

[3] Univ Toulouse III Paul Sabatier, Ctr Hosp Univ Toulouse, Serv Epidemiol, INSERM,CERPOP, Toulouse, France

[4] Univ Toulouse III Paul Sabatier, Ctr Hosp Univ Toulouse, Inst Univ Canc Toulouse Oncopole, Toulouse, France

[5] Inst Paoli Calmettes, Marseille, France

[6] Hosp Civils Lyon, Serv Hematol Clin, Hop Lyon Sud, Pierre Benite, France

[7] CHRU Jean Minjoz, Serv Hematol, F-25000 Besancon, France

[8] CHU Nancy Brabois, Serv Hematol, F-54500 Vandoeuvre Les Nancy, France

[9] CHU Henri Mondor, Serv Hematol Clin & Therapie Cellulaire, 1 Rue Gustave Eiffel, F-94010 Creteil, France

[10] Ctr Hosp Versailles, Serv Hematol, Le Chesnay, France

[11] CHU Angers, Serv Malad Sang, F-49000 Angers, France

[12] Nantes Univ, CRCI2NA, CNRS UMR 6075,Univ Angers, Inserm UMR 1307,Federat Hosp Univ Grand Ouest Leu, F-49000 Angers, France

[13] Ctr Hosp Cote Basque, Serv Hematol, F-64100 Bayonne, France

[14] Univ Paris Saclay, Dept Hematol, Gustave Roussy, Villejuif, France

[15] Nantes Univ Hosp, Hematol Dept, Nantes, France

[16] CHU Rennes, Serv Hematol Clin, F-35000 Rennes, France

[17] Hop La Pitie Salpetriere, Serv Hematol, Paris, France

[18] Hop Meaux, Serv Hematol, Meaux, France

[19] CHU Limoges, Serv Hematol Clin & Therapie Cellulaire, F-87000 Limoges, France

[20] Univ Cote Azur, Dept Hematol Clin, CHU Nice, Nice, France

[21] Nimes Univ Hosp, Dept Hematol, Nimes, France

[22] Ctr Hosp Univ Reims, Hop Robert Debre, Reims, France

[23] CHU St Etienne, Serv Hematol Clin & Therapie Cellulaire, F-42000 St Etienne, France

[24] CHRU Tours, Hematol & Therapie Cellulaire, Tours, France

[25] Ctr Hosp Sud Francilien, Serv Hematol Clin, Corbeil Essonnes, France

[26] CHU Dijon, Serv Hematol Clin, Dijon, France

[27] CHU Grenoble Alpes, Grenoble, France

[28] CHU Caen, IHBN, Serv Hematol Clin, Caen, France

[29] Ctr Hosp Rene Dubos, Serv Hematol & Therapie Cellulaire, Cergy Pontoise, France

[30] CH Roubaix, Serv Hematol, F-59100 Roubaix, France

[31] CH Avignon, Serv Oncohematol, Avignon, France

[32] CHU Brest, Hop Morvan, Serv Cancerol Hematol, Brest, France

[33] CHU Clermont Ferrand, Serv Hematol Clin & Therapie Cellulaire, Clermont Ferrand, France

[34] Univ Clermont Auvergne, EA 7453 CHELTER, Clermont Ferrand, France

[35] CHR Metz Thionville, Hop Mercy, Serv Hematol, Metz, France

[36] CHU Montpellier, Hop St Eloi, Serv Hematol Clin, F-34295 Montpellier, France

[37] Ctr Hosp Le Mans, Dept Haematol, Le Mans, France

[38] Univ Paris Cite, Hop Necker Enfants Malad, Assistance Publ Hop Paris, Serv Hematol Adultes, Paris, France

[39] CHT Troyes, Serv Hematol Clin, F-10000 Troyes, France

[40] Nantes Univ Hosp, Hematol Biol, Nantes, France

来源：

LEUKEMIA | 2023年 / 37卷 / 01期

关键词：

FLT3; MUTATIONS; CYTOGENETICS; DIAGNOSIS;

D O I：

10.1038/s41375-022-01742-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG >= 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.

引用

页码：91 / 101

页数：11

共 25 条

[1] Gilteritinib Can be Safely Combined with Atezolizumab for the Treatment of Relapsed or Refractory FLT3-Mutated AML: Results of a Phase 1 Study
Altman, Jessica K.
Bhatnagar, Bhavana
Abedin, Sameem
Przespolewski, Amanda
Patel, Prapti A.
Schiller, Gary J.
Gill, Stanley
Patel, Dhruva
Fan, Linyi
Tiu, Ramon V.
Strickland, Stephen A.
[J]. BLOOD, 2021, 138
[2] The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia
Arber, Daniel A.
Orazi, Attilio
Hasserjian, Robert
Thiele, Jurgen
Borowitz, Michael J.
Le Beau, Michelle M.
Bloomfield, Clara D.
Cazzola, Mario
Vardiman, James W.
[J]. BLOOD, 2016, 127 (20) : 2391 - 2405
[3] Genomics of Acute Myeloid Leukemia Diagnosis and Pathways
Bullinger, Lars
Doehner, Konstanze
Doehner, Hartmut
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (09) : 934 - 946
[4] Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation
Cocciardi, Sibylle
Dolnik, Anna
Kapp-Schwoerer, Silke
Ruecker, Frank G.
Lux, Susanne
Blaette, Tamara J.
Skambraks, Sabrina
Kroenke, Jan
Heidel, Florian H.
Schnoeder, Tina M.
Corbacioglu, Andrea
Gaidzik, Verena, I
Paschka, Peter
Teleanu, Veronica
Goehring, Gudrun
Thol, Felicitas
Heuser, Michael
Ganser, Arnold
Weber, Daniela
Straeng, Eric
Kestler, Hans A.
Doehner, Hartmut
Bullinger, Lars
Doehner, Konstanze
[J]. NATURE COMMUNICATIONS, 2019, 10 (1)
[5] Venetoclax in Combination with Gilteritinib Demonstrates Molecular Clearance of FLT3 mutation in Relapsed/Refractory FLT3Mutated Acute Myeloid Leukemia
Daver, Naval
Perl, Alexander E.
Maly, Joseph
Levis, Mark
Ritchie, Ellen
Litzow, Mark R.
McCloskey, James
Smith, Catherine C.
Schiller, Gary J.
Bradley, Terrence
Tiu, Ramon V.
Naqvi, Kiran
Dail, Monique
Siddani, Satya
Wang, Jing
Chyla, Brenda
Lee, Paul
Altman, Jessica K.
[J]. BLOOD, 2021, 138
[6] Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
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.
[J]. BLOOD, 2017, 129 (04) : 424 - 447
[7] Dumas P-Y, 2021, CLIN CANC RES J AM A
[8] Hematopoietic niche drives FLT3-ITD acute myeloid leukemia resistance to quizartinib via STAT5-and hypoxia-dependent upregulation of AXL
Dumas, Pierre-Yves
Naudin, Cecile
Martin-Lanneree, Severine
Izac, Brigitte
Casetti, Luana
Mansier, Olivier
Rousseau, Benoit
Artus, Alexandre
Dufossee, Melody
Giese, Alban
Dubus, Pierre
Pigneux, Arnaud
Praloran, Vincent
Bidet, Audrey
Villacreces, Arnaud
Guitart, Amelie
Milpied, Noel
Kosmider, Olivier
Vigon, Isabelle
Desplat, Vanessa
Dusanter-Fourt, Isabelle
Pasquet, Jean-Max
[J]. HAEMATOLOGICA, 2019, 104 (10) : 2017 - 2027
[9] The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial
Grimwade, D
Walker, H
Oliver, F
Wheatley, K
Harrison, C
Harrison, G
Rees, J
Hann, I
Stevens, R
Burnett, A
Goldstone, A
[J]. BLOOD, 1998, 92 (07) : 2322 - 2333
[10] The AML microenvironment catalyzes a stepwise evolution to gilteritinib resistance
Joshi, Sunil K.
Nechiporuk, Tamilla
Bottomly, Daniel
Piehowski, Paul D.
Reisz, Julie A.
Pittsenbarger, Janet
Kaempf, Andy
Gosline, Sara J. C.
Wang, Yi-Ting
Hansen, Joshua R.
Gritsenko, Marina A.
Hutchinson, Chelsea
Weitz, Karl K.
Moon, Jamie
Cendali, Francesca
Fillmore, Thomas L.
Tsai, Chia-Feng
Schepmoes, Athena A.
Shi, Tujin
Arshad, Osama A.
McDermott, Jason E.
Babur, Ozgun
Watanabe-Smith, Kevin
Demir, Emek
D'Alessandro, Angelo
Liu, Tao
Tognon, Cristina E.
Tyner, Jeffrey W.
McWeeney, Shannon K.
Rodland, Karin D.
Druker, Brian J.
Traer, Elie
[J]. CANCER CELL, 2021, 39 (07) : 999 - +

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