RESUMO
BACKGROUND: The optimal approach to combine gemtuzumab-ozogamicin (GO) with various chemotherapy backbones and other newer agents safely remains to be determined. MATERIALS AND METHODS: We performed a retrospective analysis of the safety and outcomes of adult patients with newly diagnosed acute myeloid leukemia (AML) treated with GO with intensified versus standard anthracycline doses (daunorubicin dose 90 mg/m2 vs 60 mg/m2) ± FLT3 inhibitors. The χ2 test and Mann-Whitney U test were used to compare categorical and continuous data. Survival estimates were calculated by Kaplan-Meier method and survival comparisons made using log-rank test. RESULTS: We report a 97% overall response rate in 34 patients with newly diagnosed AML with a median age of 54 years (19-75 years) treated with GO and standard induction. The 11 patients (100%) receiving GO plus daunorubicin dose 90 mg/m2 as part of 7 + 3 induction achieved complete response versus 91% (20/22) complete response in the standard daunorubicin dose group (P = NS). No increased toxicity was noted with the higher daunorubicin dose or when GO and 7 + 3 were combined with FLT3 inhibitors in 3 younger patients (<60 years). Two older patients treated with GO+7 + 3 and FLT3i experienced grade 3 or higher cardiotoxicity. We observed a longer estimated event-free survival for patients with newly diagnosed AML in our cohort (median, 24 months; 95% confidence interval, 17.2 to not reached) compared with historical data. CONCLUSION: We demonstrate that anthracycline dose intensification with GO may offer higher response rates without increased toxicity in younger patients presenting with de novo AML across European Leukemia Net risk categories.
Assuntos
Gemtuzumab/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Feminino , Gemtuzumab/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Anemia Aplástica/genética , Biomarcadores/análise , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Anemia Aplástica/patologia , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/patologia , Prognóstico , Adulto JovemRESUMO
Acute myeloid leukemia (AML) in older patients is often associated with biologic and clinical characteristics that predict poor outcomes to cytarabine and anthracycline based induction chemotherapy (IC). The impact of hypomethylating agents (HMA) in the treatment of these high-risk patients is unknown. Here we retrospectively examined the remission rates and survival outcomes of 201 newly diagnosed patients ≥60 years old with therapy-related (t-AML), secondary (s-AML), or AML with myelodysplasia-related changes (AML-MRC). Ninety-eight patients received IC, and 103 received HMA. Patients in the IC cohort were younger than those who received HMA (68 vs. 74 years; p < 0.01) with lower comorbidity burden. Composite complete remission rates (CR) were 39% in IC and 27% in the HMA cohorts (p = 0.10). Overall survival (OS) was not significantly different between the two cohorts (7.59 mos vs. 5.49 mos; HR 0.75 95% CI 0.55-1.02) despite the fact that more patients in the IC cohort (33% versus 5%, p < 0.01) underwent allogeneic stem cell transplant. Patients with t-AML (HR 0.56; 95% CI 0.33-0.97) and complex karyotype without monosomal karyotype (CK + MK-; HR 0.37; 95% CI 0.19-0.75) had better OS following IC. Patients with CK + MK+ (HR 2.00; 95% CI 1.08-3.70) had improved OS following HMA. Our results support the use of HMA as an alternative upfront regimen in older individuals with newly diagnosed high-risk AML based on similar clinical outcomes to IC.