Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S304 analysis, WT-1 gene expression was positively correlated with CD28, CD40, CD44, CD48, CD80, CD70, CD27, CD86. In survival analysis, poorer overall survival was seen in patients having higher WT-1 gene expression. Conclusions: Increased expression of the WT-1 gene positively correlates with the leukemic burden in most cases of AML. The gene can be considered a promising molecular marker for early diagnosis, MRD detection, and a target for developing novel therapeutic approaches against AML. Funding Acknowledgement: SERB, DST, Government of India Keywords: AML, WT1 gene, real-time PCR AML-469 Ivosidenib + Azacitidine vs Placebo + Azacitidine in Patients With Newly‑Diagnosed Acute Myeloid Leukemia: Updated Long‑term Efficacy and Safety Results From the AGILE Study Stéphane de Botton MD1, Pau Montesinos MD2, Susana Vives Polo MD3, Ewa Zarzycka MD4, Jianxiang Wang MD5, Marta Riva MD6, Michael Heuser MD7, Rodrigo T. Calado MD8, Andre C. Schuh MD9, Su-Peng Yeh MD10, Jianan Hui PhD11, Diego A. Gianolio PhD11, Prapti Patel MD11, Christian Recher MD12, Hartmut Döhner MD13 1Institut Gustave Roussy, Villejuif, France. 2Hospital Universitari i Politècnic La Fe, València, Spain. 3Hospital Universitario Germans Trias i Pujol-ICO Badalona, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain. 4Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland. 5Institute of Hematology & Hospital of Blood Disease – Peking Union Medical College, Tianjin, China. 6Department of Hematology, Oncology and Molecular Medicine, Ospedal Niguarda, Milan, Italy. 7Hannover Medical School, Hannover, Germany. 8Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil. 9Princess Margaret Cancer Centre, Toronto, Canada. 10China Medical University, Taichung, Taiwan. 11Servier Pharmaceuticals LLC, Boston, USA. 12Institut Universitaire du Cancer de Toulouse Oncopole, CHU de Toulouse, Toulouse, France. 13Ulm University Hospital, Ulm, Germany Context: In the AGILE study, ivosidenib (IVO) plus azacitidine (AZA) significantly improved event-free survival, overall survival (OS), complete remission (CR), and CR or CR with partial hematologic recovery (CR/CRh) rates vs placebo (PBO) plus AZA in patients with newly-diagnosed mutant IDH1 acute myeloid leukemia. Median OS (mOS) at March 2021 was 24 months (IVO-AZA) vs 7.9 months (PBO-AZA; hazard ratio [HR]: 0.44; P=0.0005). Objective: Report long-term follow-up data (June 2022). Design: Double-blind phase III study (NCT03173248). Interventions: Once daily oral IVO 500 mg (or PBO) plus AZA 75 mg/m2 (subcutaneous or intravenous) for 7 days in 28-day cycles. Outcomes: OS, blood count recovery, transfusion independence, safety. Results: Median treatment duration: 10.8 months (IVOAZA, n=73) vs 3.2 months (PBO-AZA, n=75). After March 2021, 5 patients crossed over from PBO-AZA to IVO-AZA; no adjustment was made for crossover in the updated OS analysis. At a median follow-up of 28.6 months, mOS was 29.3 months (95%confidence interval [95%CI]: 13.2–not reached) for IVO-AZA vs 7.9 months (95%CI: 4.1–11.3) for PBO-AZA (HR 0.42 [95%CI: 0.27–0.65]; P<0.0001). At 12 months, OS rates were 62.9% (IVO-AZA) and 38.3% (PBO-AZA); at 24 months, OS rates were 53.1% (IVO-AZA) and 17.4% (PBO-AZA). Hemoglobin levels increased steadily from baseline (88.8 g/L) to cycle 8 in the IVO-AZA group, then stabilized. Additionally, mean platelet count recovered from 72.7x109/L at baseline to 171.9x109/L at week 8, then remained stable. Conversion from baseline red blood cell and/or platelet transfusion dependence to post-baseline transfusion independence was 53.8% vs 17.1% (P=0.0004) for IVO-AZA vs PBO-AZA, respectively. Neutropenic fever events (27.8% vs 33.8%) and infections (34.7% vs 51.4%) were less common in those who received IVO-AZA vs PBO-AZA, respectively. Treatment-emergent adverse events leading to treatment discontinuation occurred in 26.4% (IVO-AZA) and 25.7% (PBOAZA) of patients. Conclusions: Over a follow-up period of ~2 years, OS with IVO-AZA was significantly longer than with PBOAZA. Hemoglobin and platelet counts recovered steadily with IVO-AZA. Transfusion independence was significantly increased and safety outcomes were more favorable with IVO-AZA vs PBOAZA. Funding: Agios Pharmaceuticals, Inc; Servier acquired Agios’ oncology business. Also presented at ASCO2023. Editing: Christine Ingleby, supported by Servier Pharmaceuticals LLC. Keywords: AML, ivosidenib, acute myeloid leukemia, AGILE, mutant IDH1, azacitidine, phase III AML-475 Activity, Tolerability, and Resistance Profile of the Menin Inhibitor Ziftomenib in Adults With Relapsed/Refractory NPM1‑Mutated AML Harry Erba MD, PhD1, Eunice Wang MD2, Ghayas Issa MD3, Jessica Altman MD4, Pau Montesinos MD, PhD5, Stephane DeBotton MD, PhD6, Roland Walter MD, PhD, MS7, Kristin Pettit MD8, Stephen Strickland MD, MSCI9, Mrinal Patnaik MBBS10, Marina Kremyanskaya MD, PhD11, Maria Baer MD12, James Foran MD13, Gary Schiller MD14, Lionel Ades MD, PhD15, Mael Heiblig MD16, Celine Berthon MD17, Jolanta Grembecka PhD8, Tomasz Cierpicki PhD8, Bradley Clegg BS8, Pierre Peterlin MD18, Eduardo Rodriguez Arboli MD, MPhil19, Olga Salamero MD20, Cristina Papayannidis MD, PhD21, Kun Nie PhD22, Julie Mackey Ahsan MS22, Marilyn Tabachri RN, BSN22, Daniel Corum PhD22, Mollie Leoni MD22, Stephen Dale MD22, Amir Fathi MD23 1Duke Cancer Institute, Durham, USA. 2Roswell Park Comprehensive Cancer Center, Buffalo, USA. 3The University of Texas MD Anderson Cancer Center, Houston, USA. 4Northwestern University - Robert H. Lurie Comprehensive Cancer Center, Chicago, USA. 5Hospital Universitari i Politècnic La Fe, Valencia, Spain. 6Institut Gustave Roussy Service d’Hématologie Clinique, Paris, France. 7Fred Hutchinson Cancer Research Center, Seattle, USA. 8University of Michigan, Ann Arbor, USA. 9Sarah Cannon Research Institute,
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