Real‐World Outcomes of <scp>FLAG</scp> ‐Ida Regimen in 1079 Adult Patients With First Relapsed/Refractory <scp>AML</scp> : A <scp>PETHEMA</scp> Study

In a large multicenter real-world cohort, we aimed to evaluate outcomes of FLAG-Ida salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) and validated the SALFLAGE prognostic score. We analyzed 1079 adults with R/R AML treated across 112 PETHEMA institutions over 26 years (1998-2024), including patients with primary refractory disease (36.9%) and first relapse episode (63.1%), with a median age of 52 years. Complete remission composite (CRc) was achieved 56.8%, including complete remission (CR) in 51.0%, CR with incomplete recovery in 4.0%, and morphological-free-state in 1.8%, enabling 35.2% of patients and 62% of responders to proceed to allogeneic transplantation without morphological disease. With median follow-up of 50.9 months, median overall survival (OS) was 10.2 months, with 5-year OS rate of 21.6%. Prior allogeneic transplantation (HR 0.54; p < 0.001) and relapse-free interval ≥ 1 year (HR 0.75; p = 0.024) independently predicted improved OS, whereas modified high-risk cytogenetics including t(8; 21) (HR 3.58; p < 0.001), FLT3-ITD mutation at primary diagnosis (HR 1.61; p < 0.001), and age ≥ 60 (HR 1.43; p < 0.001) conferred inferior OS. Validation of the SALFLAGE score demonstrated moderate discrimination (C-index 0.67), with 5-year survival of 38.4%, 27.2%, and 12.7% across risk categories (p < 0.001). Outcomes improved over periods (1998-2005 vs. 2006-2016 vs. 2017-2024): 30-day mortality was 6.9% vs. 9.3% vs. 5.0%, respectively (p = 0.030), and median OS was 7.8 versus 9.4 versus 11.1 months, respectively (p = 0.16). We confirm FLAG-Ida as a reference salvage regimen in fit R/R AML and validate the SALFLAGE score in this setting.

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Journal
American Journal of Hematology
Published
2026-04-22
DOI
https://doi.org/10.1002/ajh.70340
Primary Topic
Acute Myeloid Leukemia Research
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article
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article

Real‐World Outcomes of FLAG ‐Ida Regimen in 1079 Adult Patients With First Relapsed/Refractory AML : A PETHEMA Study

Gaspar Aspas Requena, Pau Montesinos, Gabriela Rodríguez‐Macías, Olga Salamero et al.
American Journal of Hematology
Acute Myeloid Leukemia Research
article

Real‐World Outcomes of FLAG ‐Ida Regimen in 1079 Adult Patients With First Relapsed/Refractory AML : A PETHEMA Study

Gaspar Aspas Requena, Pau Montesinos, Gabriela Rodríguez‐Macías, Olga Salamero, Rebeca Rodríguez‐Veiga, Marta Valero Núñez, Mar Tormo, Jorge Labrador Gómez, David Martínez‐Cuadrón, Pedro Chorão, Raimundo García Boyero, Eliana Vale Aguiar, Belén Vidriales Vicente, Isabel Cano‐Ferri, Tamara Castaño, Pilar Herrera Puente, Francisco Ibáñez Alís, Eduardo Rodríguez‐Arbolí, Marcela Espinoza, Francisca Bass, Antonio Solana‐Altabella, Manuel Barrios García, Carlos Cerveró, María García‐Fortes, Patricia García Ramírez, Susana Vives, Lorenzo Algarra-Algarra, Josefina Serrano López, Celina Benavente, Guiomar Bautista, J Burgués, Marta Polo, Fernanda Trigo, María Luz Amigo, Christine Rojas, ANA Yurena Oliva Hernandez, Manuel Pérez‐Encinas, Cristina Gil, Carlos Rodriguez‐Medina, Teresa del Bernal del Castillo, Miguel López, María L. Amador Barciela, Mercedes Colorado, Eva Barragan, Carmen Botella, Claudia L. Sossa Melo, María D. Madrigal, Mónica A. Romero Riquelme, María J. Sayas Lloris
article en

Abstract

In a large multicenter real-world cohort, we aimed to evaluate outcomes of FLAG-Ida salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) and validated the SALFLAGE prognostic score. We analyzed 1079 adults with R/R AML treated across 112 PETHEMA institutions over 26 years (1998-2024), including patients with primary refractory disease (36.9%) and first relapse episode (63.1%), with a median age of 52 years. Complete remission composite (CRc) was achieved 56.8%, including complete remission (CR) in 51.0%, CR with incomplete recovery in 4.0%, and morphological-free-state in 1.8%, enabling 35.2% of patients and 62% of responders to proceed to allogeneic transplantation without morphological disease. With median follow-up of 50.9 months, median overall survival (OS) was 10.2 months, with 5-year OS rate of 21.6%. Prior allogeneic transplantation (HR 0.54; p < 0.001) and relapse-free interval ≥ 1 year (HR 0.75; p = 0.024) independently predicted improved OS, whereas modified high-risk cytogenetics including t(8; 21) (HR 3.58; p < 0.001), FLT3-ITD mutation at primary diagnosis (HR 1.61; p < 0.001), and age ≥ 60 (HR 1.43; p < 0.001) conferred inferior OS. Validation of the SALFLAGE score demonstrated moderate discrimination (C-index 0.67), with 5-year survival of 38.4%, 27.2%, and 12.7% across risk categories (p < 0.001). Outcomes improved over periods (1998-2005 vs. 2006-2016 vs. 2017-2024): 30-day mortality was 6.9% vs. 9.3% vs. 5.0%, respectively (p = 0.030), and median OS was 7.8 versus 9.4 versus 11.1 months, respectively (p = 0.16). We confirm FLAG-Ida as a reference salvage regimen in fit R/R AML and validate the SALFLAGE score in this setting.

American Journal of Hematology
Universidad de Salamanca (ES), Université de Montpellier (FR), Universidade de Santiago de Compostela (ES), Clínica Alemana (CL), Hospital General Universitario Gregorio Marañón (ES), Hospital Clínico San Carlos (ES), Hospital de São João (PT), Hospital Universitari i Politècnic La Fe (ES), Research Institute Hospital 12 de Octubre (ES), Hospital Universitario Nuestra Señora de Candelaria (ES), Hospital Universitario Virgen Macarena (ES), Hospital General Universitario Morales Meseguer (ES), Hospital Virgen de la Luz (ES), Centre Hospitalier Universitaire de Montpellier (FR), Hospital Clínico Universitario de Valencia (ES), Complejo Hospitalario Universitario de Santiago (ES), Hospital Universitario de Gran Canaria Doctor Negrín (ES), Hospital del Salvador (CL), Complejo Hospitalario de Salamanca (ES), Marqués de Valdecilla University Hospital (ES), Hospital Universitario 12 De Octubre (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Hospital Universitario Príncipe de Asturias (ES), Hospital Regional Universitario de Málaga (ES), Hospital San Pedro de Alcántara (ES), Hospital Universitario de Burgos (ES), Hospital Arnau de Vilanova (ES), Leitat Technological Center (ES), Hospital Regional de Concepción (CL), Hospital Universitario Reina Sofía (ES), Hospital General Universitari de Castelló (ES), Hospital Universitario Doctor Peset (ES), Vall d'Hebron Hospital Universitari (ES), Hospital General Universitario De Valencia (ES), Hospital Universitario Fundación Jiménez Díaz (ES), Hospital Universitario Central de Asturias (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Hospital Dr. Gustavo Fricke (CL), Hospital General Universitario de Albacete (ES), Foscal Hospital (CO), Hospital Universitario Virgen del Rocío (ES), Hospital Universitari Germans Trias i Pujol (ES), Clínica Dávila (CL), Hospital Clínico Universitario Virgen de la Victoria (ES), Hospital Universitario Ramón y Cajal (ES), Hospital Montecelo (ES), Instituto de Investigación Sanitaria La Fe (ES)
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