RESUMO
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.
Assuntos
Nucleotídeos de Adenina/uso terapêutico , Envelhecimento , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Vidarabina/análogos & derivados , Nucleotídeos de Adenina/efeitos adversos , Nucleotídeos de Adenina/economia , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Arabinonucleosídeos/efeitos adversos , Arabinonucleosídeos/economia , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/economia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Doença Hepática Induzida por Substâncias e Drogas/terapia , Clofarabina , Estudos de Coortes , Terapia Combinada/economia , Redução de Custos , Custos e Análise de Custo , Citarabina/efeitos adversos , Citarabina/economia , Citarabina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/economia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Custos Hospitalares , Humanos , Incidência , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/economia , Tempo de Internação , Leucemia Mieloide Aguda/economia , Leucemia Mieloide Aguda/mortalidade , Michigan/epidemiologia , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/economia , Neutropenia/mortalidade , Neutropenia/terapia , Pontuação de Propensão , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Vidarabina/efeitos adversos , Vidarabina/economia , Vidarabina/uso terapêuticoRESUMO
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.