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

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.