Detalle Publicación

A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia

Autores: Vives, S.; Martinez Cuadron, D.; Bergua Burgues, J.; Algarra, L.; Tormo, M.; Martinez Sanchez, M. P. ; Serrano, J.; Herrera, P.; Ramos, F.; Salamero, O.; Lavilla, E.; Lopez Lorenzo, J. L. ; Gil, C.; Vidriales, B.; Falantes, J. F. ; Serrano, A.; Labrador, J.; Sayas, M. J.; Foncillas, M. A.; Amador Barciela, M. L. ; Olave, M. T.; Colorado, M.; Gascon, A.; Fernandez, M. A.; Simiele, A.; Perez Encinas, M. M.; Rodriguez Veiga, R.; Garcia, O.; Martinez Lopez, J.; Barragan, E.; Paiva, Bruno; Sanz, M. A.; Montesinos, P.; PETHEMA Group
Título de la revista: CANCER
ISSN: 0008-543X
Volumen: 127
Número: 12
Páginas: 2003 - 2014
Fecha de publicación: 2021
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.