Characteristics and clinical outcomes of ND-AML patients with bcor/bcorl1 mutations

Abstract 1.Background: Acute myeloid leukemia (AML) remains a challenging hematologic malignancy with heterogeneous genetic and clinical features. BCOR and BCORL1 mutations, occurring in approximately 3-5%[1] of AML cases, have been classified as adverse prognostic markers together with other secondary-type mutations in some risk stratification systems. Yet there is different opinions on the prognostic meaning of BCOR/BCORL1 mutations in AML, the clinical implications of BCOR and BCORL1 remain incompletely understood, underscoring the need for further investigation to optimize treatment approaches.Methods We conducted a retrospective multi-center study including patients with BCOR and/or BCORL1 mutated ND-AML who were consecutively treated at ECLA between August 2018 and April 2025. Patient demographics, disease characteristics , co-mutations, treatment related variables and survival outcomes were extracted. For efficacy analysis, the patients were divided into VA-based cohort, “7+3”cohort, HMA+chemo cohort and Target+chemo cohort.Findings Patients characteristics: 160 patients were enrolled (aged18-91 years; median 60 years), of which 76/160 cases were male, 84/160 cases were female. Patients in the VA-base cohort were older than those in the “7+3” cohort (Median age: 65 vs 47).The median white blood count was 5.34*10^9/l, median HGB was 75.5g/l, and median platelet count was 54*10^9/l. The median bone marrow blast cell proportion was 51.2%. Most patients(116/160) were with normal karyotypeMutational landscape in AML with BCOR/BCORL1 mutations: BCOR/BCORL1 mutations were found to be most highly associated with mutations in DNMT3A, NRAS, FLT3, RUNX1, IDH2, TET2, ASXL1, NPM1, IDH1, U2AF1 genes.Efficacy observation: After one cycle of treatment, 54.5%(72/132)patients reached cCR in total, 68.9%(31/49) patients reached cCR in VA-based cohort, 44.7% (12/26)patients reached cCR in “7+3”cohort, 46.2% (12/26)patients reached cCR in HMA+chemo cohort, and 53.8% (7/13)patients reached cCR in target+chemo cohort. The patients treated with VA-based regimen got a significantly higher cCR than “7+3”group(P = 0.046) .Survival analysis: With a median follow-up of 9 months, the median overall survival (OS) was 27months. With a median follow-up of 8.6 months, the median relapse-free survival (RFS) was 15 months in total. There was no significant difference between different treatment cohort.Conclusion BCOR/BCORL1-mutated AML were highly associated with DNMT3A, NRAS, FLT3, RUNX1, IDH2, TET2, ASXL1, NPM1, IDH1, U2AF1 co-mutations. VA-based treatment significantly increased the cCR than “7+3” regimen, yet the higher remission rate didn't turn into survival benefit. Part of the reason for this situation is the age shift between the two groups. 1.Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374(23):2209–2221.