Mutation patterns and prognostic implications in acute myeloid leukemia with chromosomal 7 deletions.

6547 Background: Chromosomal 7 deletions (del7/7q) are the most common adverse cytogenetic event in acute myeloid leukemia and are associated with high rate of relapse. We analyzed gene mutation profiles in del7/7q AML patients who relapsed after initial remission to identify molecular patterns associated with clinical outcomes. Methods: Out of 351 newly diagnosed AML patients with del7/7q, 115 (32%) achieved complete remission after first-line treatment between 2012-2023. Of the 115 patients, 77 (67%) patients relapsed during the study follow-up. Kaplan-Meier and Cox regression were used to analyze survival outcomes. Next-generation sequencing was performed on a targeted panel of 81 genes for 59 patients who relapsed on bone marrow samples at diagnosis and relapse for paired analysis. Results: The median age of the 115 patients at diagnosis was 74 (41-93). Thirty-four patients (30%) received intensive treatment. With 30.8-month median follow-up, the median overall survival (OS) was 10.4 months, with improved survival in patients without TP53 mutation (13.04 vs. 8.6 months, p=0.005) or complex karyotype (12.4 vs. 8.6 months, p=0.03). The median duration of response for the 77 patients who relapsed was 5 months (2-7). Allo-HSCT significantly improved median OS (not reached vs. 8.5 months, P=6e-06), and was identified as the key variable impacting survival in multivariate analysis. TP53 was the most commonly mutated gene at diagnosis (67%) and relapse (71%). Mutations in CBLC and KDM6A were cleared after induction therapy, while BCOR and BCORL1 were commonly acquired at relapse (Table). At diagnosis, a lower co-mutation burden was observed in TP53 mutant patients as compared with wild type (average 1.84 vs. 3.65 respectively, p=0.0001). Patients with mutated TP53 and coexisting mutations in GATA2, NF1, BCORL1, or RUNX1 at diagnosis had shorter relapse free survival (RFS, 2 vs. 5 months, p=0.01) and OS (7.2 vs. 10.4 months, p=0.01) compared to patients with solely mutated TP53 (HR 2.2; 95% CI 1.2-4; P = 0.004). Allo-HSCT significantly improved the OS in patients with mutated TP53 (13 vs. 8 months, p=0.01). Conclusions: Mutated TP53 clones persist from diagnosis to relapse in patients with del7/7q AML. In patients with mutated TP53, co-occurring mutations in GATA2, NF1, BCORL1or RUNX1 at diagnosis were linked to a shorter RFS and indicate a particularly high-risk subgroup that require proceeding to allo-HSCT in CR1 without delay. Table: see text