Exploring variables associated with prolonged survival in AML with TP53 aberration.

e18519 Background: Acute myeloid leukemia (AML) with TP53 aberration is associated with poor survival and therapeutic refractoriness, with median overall survival ranging 2-10 months. Given this wide range of mortality, this study is aimed to evaluate variables that may be associated with relatively improved prognosis in this cohort, to prospectively identify such patients and ultimately optimize management. Methods: We retrospectively analyzed 87 patients who were >18 years old with AML and TP53 aberrations at diagnosis that were treated at our institution from 2013 to 2024, separated into 2 cohorts based on survival greater or less than 6 months. Data collected included demographics, genetic characteristics, therapies, response, and overall survival. Fisher’s exact and two sample T-test was used in analysis. Results: 45 patients had overall survival of < 6 mos (median 82 days, PFS 73 days) and 42 had survival of > 6 mos (median 498 days, PFS 258 days) from time of diagnosis. There were no differences in age, sex, race, performance status, or history of prior malignancy. Caucasian patients were over-represented with TP53 mutations compared to all AML patients at our institution (p=0.0506). In the >6-month mortality group, more patients received a transplant (21.4% vs 0%, p=0.0009), as well as developed clonal evolution in those with relapse/refractory disease (42.9% vs 13.3%, p=0.0035). There were no differences in TP53 allelic burden (p=0.1712) or other molecular abnormalities (Table 1). Patients were equally likely to respond to conventional chemotherapy as hypomethylating agents (HMA). The addition of venetoclax did not improve survival compared to HMA alone (p=0.5230). The most frequent cause of death was disease progression. Conclusions: AML with TP53 aberration confers adverse risk; however, there is significant inter-patient variability with a small subset attaining long-term survival and even cure. While prospective identification of this population remains elusive, our data suggests allelic burden or multi-hit status with other poor risk cytogenetic markers may not independently predict survival in complex and heterogenous real-world populations. There is a higher proportion of white individuals in the TP53 population which may be related to underling genetic predisposition as opposed to other races, which warrants further exploration. It is unclear whether choice of therapy can be based on these findings. Stem cell transplant should be considered for appropriate patients. With detailed molecular testing and novel agents evolving in AML, future studies are essential in understanding prognosis and therapies in this difficult to treat population. Concurrent genetic abnormalities with TP53 mutation. TP53 Assoc. w/ < 6 Month (n=45) >6 Month (n=42) P-value Chr 17 del 12 10 0.8089 Complex Karyotype 24 19 0.5223 Signaling Regulator Mutation 27 19 0.2005 Epigenetic Mutation 17 14 0.8230 Transcription Factor Mutation 7 11 0.2917 RNA process Mutation 4 4 >0.9999 Cohesin Mutation 0 2 0.2302