AML-488 Impact of Somatic Mutations on Treatment Response and Outcomes in Patients With Core Binding Factor Acute Myeloid Leukemia

Abstract

Prognostic significance of somatic mutations remains unclear in patients with core binding factor acute myeloid leukemia (CBF-AML), especially with advanced next generation sequencing (NGS) and measurable residual disease (MRD) detection techniques. To estimate the distribution of mutations and to assess their impact on outcomes in CBF-AML. Single-center retrospective study Patients: Adults with newly diagnosed CBF-AML Main Outcome Measures: MRD negativity, relapse free survival, overall survival Results: Our study includes 59 patients (mean age- 48 years) with CBF-AML [t(8;21), n=21 and Inv(16), n=38], with available NGS and CBF-MRD results during primary treatment. Most common mutations at diagnosis included KIT (31%), NRAS (26%), KRAS (15%), FLT3-TKD (11%), and FLT3-ITD (9%). Mutations in NRAS were enriched (32%) in Inv(16) AML, whereas KIT mutations were common (45%) in association with t(8;21). No pathogenic mutation was noted in 17% of patients. Most common induction regimen was "7+3" (48%), followed by "7+3+GO" (37%), with 36% receiving gemtuzumab ozogamicin (GO) in consolidation (median- 3 cycles). CBF-MRD negativity was 15% at the end of induction, which increased to 70% after consolidation, with no significant difference between patients with or without common kinase mutations (KIT, RAS, or FLT3). In the t(8;21) AML, CBF-MRD negativity rate was lower in KIT-mutant vs. wild type (38% vs. 75%) patients, although it was not statistically significant (p = 0.31). Overall, 23 (39%; 14 on CR1) patients underwent allogeneic stem cell transplant (allo-SCT), with no difference in respect to baseline mutations. The rate of relapse (n = 10; 17%) was also similar with or without ≥ 1 of KIT, RAS, or FLT3 mutations. The presence of any of these 3 mutations was associated with worse relapse free survival (7.7 vs. 12.9 months; p= 0.01), with no significant difference in overall survival (median OS- 94.1 months vs. not reached, p=0.44). Overall, patients with CBF-AML did well independent of induction/consolidation regimen, inclusion of GO, achievement of MRD negativity, or allo-SCT status, with a 2-year OS of > 80%. Mutations in KIT, RAS, and FLT3 are enriched in CBF-AML and contribute to earlier relapse although OS remains favorable across molecular and treatment subgroups.