Imprimir Ver referencias Citación AMA Citation Su S, Shroff Karhade D. Su S, Shroff Karhade D Su, Shan, and Deepti Shroff Karhade. "Gilteritinib more effective than salvage chemotherapy for FLT3-mutated acute myeloid leukemia." 2 Minute Medicine, 18 noviembre 2019. McGraw-Hill, New York, NY, 2019. AccessMedicina. http://accessmedicina.mhmedical.com/updatesContent.aspx?gbosid=508323§ionid=232340945 MLA Citation Su S, Shroff Karhade D. Su S, Shroff Karhade D Su, Shan, and Deepti Shroff Karhade.. "Gilteritinib more effective than salvage chemotherapy for FLT3-mutated acute myeloid leukemia." 2 Minute Medicine New York, NY: McGraw-Hill, 2019, http://accessmedicina.mhmedical.com/updatesContent.aspx?gbosid=508323§ionid=232340945. Descargar archivo de la citación: RIS (Zotero) EndNote BibTex Medlars ProCite RefWorks Reference Manager Mendeley © Copyright Clip Capítulo completo Sólo figuras Sólo cuadros Solo Videos Supplementary Content Arriba Gilteritinib more effective than salvage chemotherapy for FLT3-mutated acute myeloid leukemia by Shan Su, Deepti Shroff Karhade Listen +Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission. +1. In this phase 3 trial, patients with relapsed or refractory acute myeloid leukemia who received gilteritinib had a longer median overall survival and a higher likelihood of complete remission versus chemotherapy. After factoring in therapy duration, serious adverse events also occurred less frequently in the gilteritinib group. +2. Despite these statistically significant improvements, long-term survival remained poor, indicating the need for further research into the timing and toxicity of intervention. +Evidence Rating Level: 1 (Excellent) Study Rundown: + +FMS-like tyrosine kinase 3 (FLT3) is involved in the proliferation and differentiation of hematopoietic stem cells. When constitutively activated through mutation as in roughly 30% of patients with acute myeloid leukemia (AML), the enzyme sparks uncontrolled growth and adversely affects survival. Given the ineffectiveness of salvage chemotherapy as a second-line treatment for AML that is refractory to standard chemotherapy, FLT3 inhibitors have been a welcome addition to the arsenal of treatment options. However, issues have arisen with their selectivity and single-agent potency, stressing the continued need for a powerful molecule that demonstrates strong activity against both mutation subtypes (ITD and TKD) yet spares other essential kinases. This randomized study aimed to confirm the safety and efficacy of one such candidate, gilteritinib, in the treatment of relapsed or refractory FLT3-mutated AML. Patients treated with gilteritinib experienced both a longer median overall survival and a higher likelihood of complete remission with full or partial hematologic recovery compared to those who received salvage chemotherapy. The exposure-adjusted rate of adverse events of grade 3 or higher was also significantly lower in the gilteritinib group, with some of the most common events in both groups being febrile neutropenia, anemia, and thrombocytopenia. However, long-term survival rates remained poor in both groups. These promising findings beg further research into the timing of FLT3 intervention as well as its role in the grand scheme of potential treatments. +Click here to read the study in NEJM +Relevant Reading: FLT3 inhibitors in acute myeloid leukemia In-Depth [randomized controlled trial]: + +This randomized phase 3 trial recruited 371 adult patients from 107 centers in 14 countries and assigned them in a 2:1 ratio to gilteritinib or chemotherapy, respectively. 60.6% of all patients had relapsed AML while the remainder had primary refractory disease. 83.8% had previously been treated with anthracyclines but not FLT3 inhibitors. Bone marrow and blood samples were collected for screening, and over 90% of patients were found to possess in tandem duplication (ITD) mutations. Overall survival for patients in the gilteritinib group was 9.3 months versus 5.6 months for those in the chemotherapy group (two-sided P<0.001; hazard ratio for death, .64; 95% confidence interval [CI], 0.49 to 0.83). 34% of patients who were administered gilteritinib had complete remission with full or partial hematologic recovery compared to 15.3% in the chemotherapy group (risk difference, 18.6 percentage points; 95% CI, 9.8 to 27.4). After 1 year, 37.1% of patients remained alive in the gilteritinib group compared to 16.7% in the chemotherapy group. This pattern of increased survival was consistent across multiple subgroups. In the gilteritinib group, treatment duration was longer and more variable (median, 18 weeks; interquartile range [IQR], 9 to 34) compared to chemotherapy (median, 4 weeks; IQR, 4 to 3). After adjusting for exposure, the incidence rate of adverse events of grade 3 or higher was 19.34/patient-year in the gilteritinib group and 42.44/patient-year in the chemotherapy group. +©2019 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.