Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S312 Results: Overall, 123 patients with NPM1+ AML and 360 patients with NPM1– AML were included. Most patients were male (NPM1+, 61.5%; NPM1−, 60.7%) and white (NPM1+, 78.0%; NPM1−, 85.6%); median (range) age was 67 (55-87) and 71 (55-97) years for the NPM1+ and NPM1− groups, respectively. After adjusting for age, patients with NPM1+ AML had significantly longer median OS than patients with NPM1– AML (26 vs 15 months; HR [95% CI]: 0.58 [0.44-0.76]; P<0.01). Patients with NPM1+ vs NPM1– AML had a lower frequency of certain key mutations, such as TP53 (1.6% vs 18.6%) and RUNX1 (0.8% vs 14.8%). The significant survival benefit with NPM1+ vs NPM1, initially observed after adjusting for age, was not observed after further adjusting for presence of TP53 and RUNX1 mutations (NPM1+ vs NPM1–; 23 vs 19 months; HR [95% CI]: 0.75 [0.48-1.17]; P=0.21). Conclusions: TP53 plus RUNX1 mutations were identified as a pattern of co-mutational burden that was observed less frequently and potentially contributed to the improved OS of patients with NPM1+ AML and poorer OS of patients with NPM1– AML. Acknowledgements: Bristol Myers Squibb (NCT01688011). © 2023 American Association for Cancer Research. Reused with permission. This abstract was accepted and previously presented at the AACR Annual Meeting 2023 Meeting. All rights reserved. Keywords: AML, acute myeloid leukemia, biomarkers, TP53, RUNX1, NPM1 AML-554 A Phase III, Randomized, Open‑Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Azacitidine in Previously Untreated Patients With TP53‑Mutant Acute Myeloid Leukemia Naval G. Daver MD1, Paresh Vyas MRCP FRCP FRCPath2, Guan Xing MD3, Camille Renard MSc3, Taravat Bagheri PharmD3, Kelly Curtis MD3, David A. Sallman MD4, Andrew H. Wei MBBS, PhD5 1The University of Texas MD Anderson Cancer Center, Houston, USA. 2Weatherall Institute of Molecular Medicine, Oxford, United Kingdom. 3Gilead Sciences, Inc., Foster City, USA. 4Moffitt Cancer Center, Tampa, USA. 5Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Melborne, Australia Introduction: Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a macrophage immune checkpoint and “don’t eat me” signal on cancer cells, that eliminates leukemia stem cells by inducing phagocytosis. Hypomethylating agents synergize with magrolimab by inducing “eat me” signals on leukemic blasts. Magrolimab with azacitidine (AZA) has shown encouraging activity in frontline acute myeloid leukemia (AML) unfit for intensive chemotherapy, including in patients with TP53 gene mutations, which are observed in 10%−15% of newly diagnosed AML and associated with poor survival. Methods: In this phase III, randomized, openlabel, multicenter study, approximately 346 adult patients with treatment-naïve TP53-mutant AML will be randomized (1:1) to magrolimab+AZA or physician’s choice of venetoclax (VEN)+AZA or “7+3” chemotherapy, based on patient fitness. Randomization will be stratified by appropriateness for non-intensive vs intensive therapy, geographic region (US vs non-US sites), and age (<75 vs ≥75 years). Patients are eligible if they have ≥1 confirmed TP53 mutation that is not benign or likely benign, or biallelic 17p deletions. During the first 28-day cycle, patients randomized to magrolimab+AZA will receive magrolimab intravenously (IV) at a priming dose of 1 mg/kg on Days 1 and 4, 15 mg/kg on Day 8, and 30 mg/kg on Days 11, 15, and then weekly for 5 doses, followed by every other week beginning 1 week after the fifth weekly dose. For patients randomized to VEN+AZA, these will be administered per labeled indications. Patients receiving 7+3 chemotherapy will undergo 1−2 induction cycle(s) with IV daunorubicin or idarubicin on Days 1−3 and cytarabine 100 mg/m2 or 200 mg/m2 on Days 1−7 followed by up to 4 consolidation cycles with high-dose cytarabine (1500 or 3000 mg/m2). Patients receiving magrolimab+AZA or VEN+AZA will continue until disease progression, relapse, loss of clinical benefit, unacceptable toxicities, or stem cell transplant. Patients can undergo stem cell transplantation per investigator decision. The primary endpoint is overall survival (OS) in patients appropriate for non-intensive therapy, and the key secondary endpoint is OS in all patients. Safety will also be evaluated. Results: Trial in progress. Conclusion: As of May 2023, patient enrollment is ongoing at 139 sites. Clinical trial information: NCT04778397. Funding: Gilead Sciences, Inc. Keywords: AML, magrolimab, azacitidine, ENHANCE-2, anti-CD47, Trial-in-Progress AML-557 Clinical Outcomes of Therapy‑Related Acute Leukemia (t‑AL): A Single‑Center Retrospective Analysis Kok Hoe Chan MD, Ji Zheng Lin MD, Binoy Yohannan MD, Adan Rios MD The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, USA Context: t-AL arises after exposure to cytotoxic chemotherapy and/or radiation therapy and is associated with poor prognosis. t-AL tends to have adverse cytogenetics, unlike acute promyelocytic leukemia (t-APL) and core-binding factor acute myeloid leukemia (t-CBF-AML), which tend to have favorable cytogenetics. Objective: Analyze the clinical outcomes of patients with t-AL treated at our institution. Design: Single-center retrospective study evaluating the clinical outcomes of patients with t-AL from 01/2013 to 12/2020. Setting: General community, academic hospital. Patients or Other Participants: Adults with t-AL. Main Outcome Measures: Clinical outcomes, complete response (CR) and minimal residual disease (MRD). Results: Among 120 patients with AL, we identified 10 cases of t-AL (9 t-AML and 1 t-ALL). Of the nine patients with t-AML, 4 had t-APL, 1 with t-CBF-AML and 4 with adverse risk per ELN 2022 risk stratification. The median age was 58.5 years and 80% were female. All 4 patients with t-APL had intracerebral hemorrhage, received all-trans retinoic acid and arsenic trioxide, and 2 received additional idarubicin as part of the induction regimen. Only one patient died during induction due to intracerebral hemorrhage, and
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