RESUMEN
The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.
Asunto(s)
Nucleótidos de Adenina/uso terapéutico , Envejecimiento , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Arabinonucleósidos/uso terapéutico , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Vidarabina/análogos & derivados , Nucleótidos de Adenina/efectos adversos , Nucleótidos de Adenina/economía , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/economía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Arabinonucleósidos/efectos adversos , Arabinonucleósidos/economía , Estudios de Casos y Controles , Enfermedad Hepática Inducida por Sustancias y Drogas/economía , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/mortalidad , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Clofarabina , Estudios de Cohortes , Terapia Combinada/economía , Ahorro de Costo , Costos y Análisis de Costo , Citarabina/efectos adversos , Citarabina/economía , Citarabina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Costos de Hospital , Humanos , Incidencia , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/economía , Tiempo de Internación , Leucemia Mieloide Aguda/economía , Leucemia Mieloide Aguda/mortalidad , Michigan/epidemiología , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/economía , Neutropenia/mortalidad , Neutropenia/terapia , Puntaje de Propensión , Estudios Retrospectivos , Análisis de Supervivencia , Centros de Atención Terciaria , Vidarabina/efectos adversos , Vidarabina/economía , Vidarabina/uso terapéuticoRESUMEN
Patients with secondary acute myeloid leukemia (sAML) have poor outcomes, with CR/CRi rates of 25-35% with standard 7â¯+â¯3 induction chemotherapy, while single center non-comparative analyses suggest promising outcomes with FLAG. We conducted a single-center, retrospective cohort study assessing outcomes in treatment-naïve patients with sAML treated with fludarabine, high-dose cytarabine, and granulocyte colony-stimulating factor (FLAG, nâ¯=â¯40) compared with 7â¯+â¯3 (nâ¯=â¯66). Median patient age was 63 years (range: 27-82) in the FLAG group and 60 years (range: 21-76) in the 7â¯+â¯3 group (Pâ¯=â¯0.968). Patients treated with FLAG achieved higher overall response rates (CRâ¯+â¯CRiâ¯+â¯MLFS) compared to 7â¯+â¯3 (70% vs. 48%, Pâ¯=â¯0.043). FLAG was well tolerated, with only one induction death (30-day mortality rate, 3% vs. 8%, Pâ¯=â¯0.405) and no cases of cerebellar toxicity. Duration of neutropenia was significantly shorter with FLAG (median 16 vs. 23â¯days, Pâ¯<â¯0.001). Half of the FLAG-treated patients proceeded to consolidative therapy compared with only 27% of those who received 7â¯+â¯3 (Pâ¯=â¯0.022). Overall survival was comparable between groups (8.5 mos, FLAG vs. 9.1 mos, 7â¯+â¯3; Pâ¯=â¯0.798). Thus, FLAG may represent a low-cost treatment strategy in sAML that produces higher response rates and promising survival outcomes with minimal treatment-related toxicity. Further studies are required to prospectively compare FLAG to the newly FDA-approved CPX-351 in sAML.