1295 Prognostic Impact of Chromosome 7 Losses in High-Grade TP53 Mutated Myeloid Neoplasms
Recommended Citation
Binte Tahir N, Venkataraman G, Rojek A, Symes E, Kaur A, Tjota M, Fitzpatrick C, Arber D, Wang P, Lager A, Perry A, Bell R, Chang H, Zhou Q, Menon M, Patel J, Patel A, Tariq H, Zhang J, Sojitra P, Nawas M, Patel A, DuVall A, Patil E, Badar T, Velmurugan S, Hasan F, Ghosh S. 1295 Prognostic Impact of Chromosome 7 Losses in High-Grade TP53 Mutated Myeloid Neoplasms. Lab Investig 2025; 105(3 Supplement).
Document Type
Conference Proceeding
Publication Date
3-1-2025
Publication Title
Lab Investig
Abstract
Background: TP53 mutation (TP53MUT) and chromosome 7 loss (-7/7q) are both independently considered as adverse prognostic factors in high-grade (HG) myeloid neoplasms (MN). Whether the co-occurrence of -7/7q further worsens the poor prognosis of TP53MUT is unclear. To answer this, we evaluated the differential impact of -7/7q in HG TP53MUT MN. Design: We identified 322 patients with TP53MUT MN carrying ≥1 TP53MUT at a VAF ≥3% diagnosed between 2014-2024 across 10 centers with blasts ≥10% at diagnosis. Baseline clinical, pathological, cytogenetic and somatic information was extracted while stratifying patients by -7/7q status. The primary endpoint was to compare 24-month overall survival (OS24). Additional end-points included complete response to first-line (CR1) therapy per ELN 2022 guidelines (Table 1 footnote). Descriptive and outcome analyses were conducted in Stata 18 using flexible parametric (FP) and non-parametric survival methods. Results: The median age at diagnosis was 68.4 years. There was no difference in baseline characteristics stratified by -7/7q status (see Table 1). Patients with -7/7q were marginally more likely to harbor complex karyotype (P = .09) with significantly greater proportion harboring -17/17p (46.2% vs. 33.8%; P = .031) and TP53 VAF>25% (85.6% vs. 76.4%; P = .042) compared to those without -7/7q. The median duration of follow up (from diagnosis of TP53MUT MN to study exit) was 6.2 months (range: 0.0–72.8 months) with 77.0% receiving frontline non-intensive therapies, mostly HMA-based. First-line response was evaluable in 251 patients with 28.7% achieving CR, 24.7% had partial response, and 46.6% had non-response/stable-progressive disease. -7/7q was not associated with inferior frontline response (P = .35) in the entire cohort as well as in the intensively-treated subgroup (P = .92). Significantly greater proportions of those lacking -7/7q went on to receive alloSCT (20.7% vs. 11.1%; P = .023). In the entire cohort OS24 analysis, -7/7q was associated with inferior overall survival (HR = 1.5 [1.2–2.0]; Pfpm = .002; N = 298). In separate analysis by blast count and therapies, the adverse impact was restricted only to those subgroups with either high blast count or intensive therapy (See figure 1). [Formula presented] [Formula presented] Conclusions: Presence of -7/7q adversely impacts the prognosis of TP53MUT MN, an effect which is accentuated in patients receiving intensive chemotherapy and ≥ 20% blast count at diagnosis, supporting its prognostic utility in this context.
Volume
105
Issue
3 Supplement
