Outcomes Of Adult Acute Myeloid Leukemia Treated With Gemtuzumab-Ozogamicin: Cue To Optimized Chemotherapy Backbone

Novel therapies are transforming care for patients with acute myeloid leukemia (AML). Chemotherapy remains a key backbone in management of fit patients with AML. The optimal approach to combine gemtuzumabozogamicin (GO) with various chemotherapy backbones and other newer agents safely remains to be defined. We performed a retrospective analysis of the safety and outcomes of newly diagnosed adult patients with AML treated with GO in combination with intensified versus standard anthracycline doses (daunorubicin dose 90 mg/m(2) vs 60 mg/m(2)) +/- FLT3 inhibitors. We report an overall response rate of 97% in patients with newly diagnosed AML (n = 37); all patients (N = 11) receiving GO plus daunorubicin dose 90 mg/m 2 as part of 7 3 induction achieved complete response without increased rates of toxicity. No increased toxicity was noted when GO and 7 3 were combined with FLT3 inhibitors were safe in younger patients; however, 2 older patients treated with GO+7 + 3 and FLT3i experienced cardiac issues. We demonstrate that anthracycline dose intensification in combination with GO+ FLT3i may offer higher response rates without increased toxicity in younger patients presenting with de novo AML across all European Leukemia Net risk categories.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/m(2) vs 60 mg/m(2)) +/- FLT3 inhibitors. The chi(2) 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/m(2) as part of 7 + 3 induction achieved complete response versus 91% (20/22) complete response in the standard daunorubicin dose group = 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. (C) 2021 Elsevier Inc. All rights reserved.