Real life treatments and outcomes of older patients aged more than 60 years with FLT3-mutated acute myeloid leukemia: Report from the multicentric french observational ALFA-PPP study
Year: 2025
Type: conference-abstract
Abstract: Introduction. Based on the results of the phase 3 RATIFY trial (Stone et al, NEJM, 2017), 7+3 (daunorubicin/cytarabine) plus midostaurin is considered the standard of treatment for acute myeloid leukemia (AML) with FLT3 mutation (ITD and TKD) in patients aged <60 years. In this trial, patients who completed the consolidation phase and were not allotransplanted received a maintenance therapy with single-agent midostaurin. In the phase 2 AMLSG 16-10 trial (Schlenk et al, Blood, 2019), the same schedule was safely administered and was shown to be effective in older patients up to 70 years. Another option for maintenance therapy in these patients is oral azacitidine (AZA) as demonstrated in a post-hoc analysis of the phase 3 QUAZAR AML-001 trial (Döhner et al, Blood, 2022). Methods.In 2022, the Acute Leukemia French Association (ALFA) group initiated a multicentric prospective observational study (ALFA-PPP, NCT04777916) aiming to collect clinical data and biosamples in all AML patients aged ≥18y referred to 27 ALFA centers. Clinical data and samples were structured by approved therapies. Here we report data on treatments and outcomes of FLT3-mutated AML cases aged ≥60y included between April 2022 and August 2024 in the multicentric French Observational ALFA-PPP study and treated upfront, with a specific focus on intensively-treated patients. Results. We analysed treatments and outcomes of 149 patients aged ≥60y. In all, 80 (53.7%) received intensive therapy (median age 68.5y, 60-78) while 60 (40.3%) underwent a non-intensive treatment, mainly AZA plus venetoclax for 81% of them (median age 77y, 64-98); 3 received best supportive care and 6 died before treatment initiation. 16 patients (10.7%) were included in a clinical trial: they were excluded from further analyses. Henceforth, our specific focus was on the 70 patients who were intensively treated outside of a clinical trial, among whom 7 were aged ≥75y. In all, 70%, 22.8% and 7.2% had a FLT3-ITD, FLT3-TKD or both mutations, respectively. For other molecular events of interest, NPM1, IDH, RAS and secondary AML-type mutations were identified in 68.5%, 21.4%, 37% and 36%, respectively. According to ELN-2022, 13%, 63% and 24% were classified as favorable, intermediate and poor-risk. Intensive approaches were as follows: 7+3 for 57 (81%), CPX-351 for 11 (16%), 7+3 plus GO for one patient (1%) and amsacrine/cytarabine for the last patient (1%). Specifically in the 7+3 subcohort, the majority received 7+3 with midostaurin (n=39, 68%; idarubicin 28, daunorubicin 11); 17 were treated without midostaurin (30%; ida 11, dauno 6). The overall complete remission rate (CR/CRi) was 62.7%. After remission, 16 patients (23%) were allotransplanted, 26 (37%) did not receive any maintenance therapy (14 because of a refractory/relapsed status, 9 died before) and 27 (38.5%) received an oral continuous maintenance therapy detailed as follows: midostaurin for 5 patients, 17 switched from midostaurin to oral AZA and 5 received gilteritinib. In the 70 intensively treated patients, overall survival (OS) was estimated at 58% (95% CI, 44-70) at 2 years. We performed a time-dependent multivariable Cox regression analysis using the following covariates in these patients: age, ECOG, HCT-CI comorbidity index, ELN-2022 risk category, NPM1, FLT3-ITD and TKD, secondary AML-type mutations, leukocyte count, maintenance therapy as a time-dependent variable with different categories (allotransplantation, FLT3 inhibitor midostaurin/gilteritinib, oral AZA, no maintenance). In this analysis, allotransplantation (HR, 0.09 [95% CI, 0.01-0.78]; p=0.029) or maintenance therapy with midostaurin/gilteritinib (HR, 0.17 [95% CI, 0.03-0.93]; p=0.041) were associated with prolonged OS, while maintenance with oral AZA was not (HR, 0.41 [95% CI, 0.12-1.43]; p=0.16). Conclusions. In the ALFA-PPP real-life cohort of FLT3-mutated AML patients aged ≥60y treated frontline, few were included in clinical trials. The majority of intensively-treated patients received intensive chemotherapy cycles plus midostaurin. However, for maintenance therapy, oral AZA was often preferred to FLT3 inhibitors while oral AZA did not significantly improve survival in the multivariable analysis. Notably, frontline allogeneic transplantation or maintenance therapy with FLT3 inhibitors significantly prolonged OS and could therefore be considered in patients who receive intensive treatment.
Source: Blood
Authors: Ramy Rahmé, Emmanuel Raffoux, Lionel Ades, Stephane De Botton, Nicolas Duployez, Alexandra COELHO, Jean-Baptiste Micol, Sylvain Chantepie, Thomas Cluzeau, Delphine Lebon, Pierre Arnautou, Mathieu Leclerc, Laure Farnault, Ollivier Legrand, Ahmad Aljijakli, Céline Berthon, Juliette Lambert, Claire Bories, Ambroise Marçais, Julia HIEULLE, Celia Salanoubat, Pascal Turlure, Kevin-James Wattebled, Benjamin Carpentier, Jamile Frayfer, Ioana Vaida, Madalina Uzunov, Reda Garidi, Luca Inchiappa, Karine Celli-Lebras, Dominique Penther, Raynier Devillier, Raphael Itzykson, Claude Preudhomme, Renaud Buffet, Herve Dombret, Thorsten Braun
Institutions: Assistance Publique – Hôpitaux de Paris, Hôpital Avicenne, Hôpital Saint-Louis, Laboratoire d'hématologie, Institut Gustave Roussy, Centre Hospitalier Universitaire de Lille, Acute Leukemia French Association, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire Amiens-Picardie, Hôpital d'instruction des Armées Percy, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, Hôpital de la Conception, Hôpital Saint-Antoine, Centre Hospitalier Victor Dupouy, Centre Hospitalier de Versailles, Centre Hospitalier de Lens, Hôpital Necker-Enfants Malades, Centre Hospitalier de Roubaix, Centre Hospitalier Sud Francilien, Centre Hospitalier Universitaire de Limoges, Hôpital NOVO, Pitié-Salpêtrière Hospital, Centre Hospitalier de Saint-Quentin, Centre Antoine Lacassagne, Centre Hospitalier Universitaire de Rouen, Centre Henri Becquerel, Institut Paoli-Calmettes
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417018986
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