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

Pierre-Yves Dumas (1) , Emmanuel Raffoux (2) , Emilie Bérard (3, 4) , Sarah Bertoli (5) , Marie-Anne Hospital (6) , Maël Heiblig (7) , Yohann Desbrosses (8) , Caroline Bonmati (9) , Cécile Pautas (10) , Juliette Lambert (11) , Corentin Orvain (12, 13) , Anne Banos (14) , Florence Pasquier (15) , Pierre Peterlin (16) , Tony Marchand (17) , Madalina Uzunov , Jamilé Frayfer , Pascal Turlure , Thomas Cluzeau , Eric Jourdan , Chantal Himberlin , Emmanuelle Tavernier , Alban Villate , Stephanie Haiat , Marie-Lorraine Chretien , Martin Carre , Sylvain Chantepie , Ioana Vaida , Mathieu Wemeau , Safia Chebrek , Gaelle Guillerm , Romain Guièze (18) , Houria Debarri , Eve Gehlkopf , Kamel Laribi , Ambroise Marcais , Alberto Santagostino , Marie-Christine Béné , Ariane Mineur , Arnaud Pigneux , Hervé Dombret , Christian Récher (5)

1 CHU Bordeaux
2 AP-HP - Hopital Saint-Louis [AP-HP]
3 Equipe Vieillissement (CERPOP)
4 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
5 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
6 IPC - Institut Paoli-Calmettes
7 HCL - Hospices Civils de Lyon
8 Service d'Hématologie [CHRU Besançon]
9 Service d'Hématologie [CHRU Nancy]
10 CHU Henri Mondor [Créteil]
11 CHV - Centre Hospitalier de Versailles André Mignot
12 CRCI2NA - Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
13 CHU Angers - Centre Hospitalier Universitaire d'Angers
14 CHCB - Centre Hospitalier de la Côte Basque
15 Département d'hématologie [Gustave Roussy]
16 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
17 Service d’Hématologie Clinique [Rennes]
18 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias

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.

Domains: Cancer; Hematology; Pharmacology

Pierre-Yves Dumas, Emmanuel Raffoux, Emilie Bérard, Sarah Bertoli, Marie-Anne Hospital, et al.. 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. Leukemia, 2023, 37 (1), pp.91-101. ⟨10.1038/s41375-022-01742-7⟩. ⟨hal-04244552⟩