Real-world outcomes of TP53-mutated acute myeloid leukemia at a single institution.

e18543 Background: TP53-mutated acute myeloid leukemia (AML) represents a high-risk subset with poor response to conventional intensive chemotherapy. Hypomethylating agents with or without venetoclax (VEN/HMA) have emerged as a major treatment option for TP53-mutated AML. This study reports real-world clinical outcomes of TP53-mutated AML at a single institution. Methods: We conducted a retrospective cohort study of adult patients with TP53-mutated AML treated at Stony Brook University Hospital between 2020 and 2025. Demographics, disease characteristics, treatments and outcomes were collected. Endpoints included time to treatment initiation (TTI) and overall survival (OS). Median follow-up was calculated using the reverse Kaplan-Meier method from date of initial biopsy to date of expiration. Results: Nineteen patients were identified; median age at diagnosis was 80 years (range 49-91). Secondary AML was present in 42% (n=7) including preceding myelodysplastic syndrome (n=5) or therapy-related AML (n=2). TP53 biallelic mutations or loss was present in 37% (n=7) and complex karyotype in 89% (n=17). Thirteen patients (68%) received therapy; median TTI was 10 days (range 5-99). First-line therapy included Venetoclax-based regimens (n=10), 7+3 intensive chemotherapy (n=1), single-agent azacitidine (n=1) and CPX-351 (n=1). Three patients treated with venetoclax-based therapy received subsequent lines of therapy upon progression. One patient ultimately underwent haploidentical allogeneic stem cell transplant with OS of 456 days. Median follow-up and median OS were both 79 days (range 6-456); all 19 patients died. Among patients receiving lower intensity therapy (n=11, including 10 venetoclax-based), median OS was 112 days, compared to 27 days in untreated patients (p=0.00108). Thirty-day mortality was lower in treated versus untreated patients (8% vs. 67%), with a larger difference at 60 days (23% vs. 83%). There was no significant difference in age or Eastern Cooperative Oncology Group (ECOG) performance status between treated and untreated patients. Among the six untreated patients, five presented with neutropenic fever and opportunistic infections, required Medical Intensive Care Unit admission, and rapidly declined while hospitalized. The remaining untreated patient could not receive transfusions due to religious beliefs. Conclusions: In this real-world limited cohort of TP53-mutated AML, outcomes remain dismal. Approximately one-third of patients did not receive AML-directed therapy due to neutropenic fever and rapid clinical decline, or inability to receive supportive care. While therapy was associated with prolonged OS, the apparent survival advantage is likely confounded by baseline disease severity rather than treatment alone. Even among treated patients, survival remained limited, and durable disease control was rare, reinforcing TP53-mutated AML as a critical area of unmet need.