Susana Vives1,2, David Martínez-Cuadrón3,4, Juan Bergua Burgues5, Lorenzo Algarra6, Mar Tormo7, María Pilar Martínez-Sánchez8, Josefina Serrano9, Pilar Herrera10, Fernando Ramos11, Olga Salamero12, Esperanza Lavilla13, José L López-Lorenzo14, Cristina Gil15, Belén Vidriales16, Jose F Falantes17, Alfons Serrano18, Jorge Labrador19, María J Sayas20, María Á Foncillas21, María L Amador Barciela22, María Teresa Olave23, Mercedes Colorado24, Adriana Gascón25, María Á Fernández26, Adriana Simiele27, Manuel M Pérez-Encinas28, Rebeca Rodríguez-Veiga3,4, Olga García1,2, Joaquín Martínez-López8, Eva Barragán3,4, Bruno Paiva29, Miguel Á Sanz3,4, Pau Montesinos3,4. 1. Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain. 2. José Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Hospital Universitari i Politècnic La Fe, Valencia, Spain. 4. Spanish Biomedical Research Centre in Cancer, Carlos III Institute, Madrid, Spain. 5. Hospital San Pedro Alcántara, Cáceres, Spain. 6. Hospital General de Albacete, Albacete, Spain. 7. Hospital Clínic de Valencia (INCLIVA), Valencia, Spain. 8. Hospital 12 de Octubre, Madrid, Spain. 9. Hospital Universitario Reina Sofía, Córdoba, Spain. 10. Hospital Ramón y Cajal, Madrid, Spain. 11. Hospital Universitario de León, León, Spain. 12. Hospital Vall d'Hebrón-VHIO, Barcelona, Spain. 13. Hospital Universitario Lucus Agusti, Lugo, Spain. 14. Fundación Jiménez Díaz, Madrid, Spain. 15. Hospital General Universitario de Alicante, Alicante, Spain. 16. Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain. 17. Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Seville, Spain. 18. Hospital Universitario HM San Chinarro, Madrid, Spain. 19. Hospital Universitario de Burgos, Burgos, Spain. 20. Hospital Doctor Peset, Valencia, Spain. 21. Hospital Universitario Infanta Leonor, Madrid, Spain. 22. Hospital Montecelo, Pontevedra, Spain. 23. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. 24. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 25. Hospital General Universitari de Castelló, Castelló, Spain. 26. Hospital Xeral Cíes, Vigo, Spain. 27. Hospital Povisa, Vigo, Spain. 28. Hospital Clínico Universitario de Santiago, A Coruña, Spain. 29. Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
Abstract
BACKGROUND: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA). METHODS: Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. RESULTS: The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). CONCLUSIONS: FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.
BACKGROUND: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA). METHODS: Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. RESULTS: The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). CONCLUSIONS: FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.
Authors: David Martínez-Cuadrón; Juan E Megías-Vericat; Josefina Serrano; Pilar Martínez-Sánchez; Eduardo Rodríguez-Arbolí; Cristina Gil; Eliana Aguiar; Juan Bergua; José L López-Lorenzo; Teresa Bernal; Ana Espadana; Mercedes Colorado; Carlos Rodríguez-Medina; María López-Pavía; Mar Tormo; Lorenzo Algarra; María-Luz Amigo; María J Sayas; Jorge Labrador; Juan I Rodríguez-Gutiérrez; Celina Benavente; Lissette Costilla-Barriga; Raimundo García-Boyero; Esperanza Lavilla-Rubira; Susana Vives; Pilar Herrera; Daniel García-Belmonte; María Mar Herráez; Graça Vasconcelos Esteves; Maria I Gómez-Roncero; Ana Cabello; Guiomar Bautista; Amaia Balerdi; José Mariz; Blanca Boluda; Miguel Á Sanz; Pau Montesinos Journal: Blood Adv Date: 2022-02-22
Authors: Jorge Labrador; Miriam Saiz-Rodríguez; Dunia de Miguel; Almudena de Laiglesia; Carlos Rodríguez-Medina; María Belén Vidriales; Manuel Pérez-Encinas; María José Sánchez-Sánchez; Rebeca Cuello; Alicia Roldán-Pérez; Susana Vives; Gonzalo Benzo-Callejo; Mercedes Colorado; María García-Fortes; María José Sayas; Carmen Olivier; Isabel Recio; Diego Conde-Royo; Álvaro Bienert-García; María Vahi; Carmen Muñoz-García; Cristina Seri-Merino; Mar Tormo; Ferran Vall-Llovera; María-Ángeles Foncillas; David Martínez-Cuadrón; Miguel Ángel Sanz; Pau Montesinos Journal: Cancers (Basel) Date: 2022-03-29 Impact factor: 6.639
Authors: Rosa Ayala; Inmaculada Rapado; Esther Onecha; David Martínez-Cuadrón; Gonzalo Carreño-Tarragona; Juan Miguel Bergua; Susana Vives; Jesus Lorenzo Algarra; Mar Tormo; Pilar Martinez; Josefina Serrano; Pilar Herrera; Fernando Ramos; Olga Salamero; Esperanza Lavilla; Cristina Gil; Jose Luis López Lorenzo; María Belén Vidriales; Jorge Labrador; José Francisco Falantes; María José Sayas; Bruno Paiva; Eva Barragán; Felipe Prosper; Miguel Ángel Sanz; Joaquín Martínez-López; Pau Montesinos Journal: Cancers (Basel) Date: 2021-05-18 Impact factor: 6.639