1266 The 20% Blast Count Threshold is Relevant in Patients with TP53-Mutated Myeloid Neoplasm Receiving Frontline Hypomethylating Agent Based Therapies
Recommended Citation
Simon R, Shao H, Mason E, Zhang J, Patwardhan P, Bailey N, Kaur A, Sojitra P, Tariq H, Forrest M, Ghosh S, Pan Z, Saygin C, Wang P, Roberts M, Perry A, Venkataraman G. 1266 The 20% Blast Count Threshold is Relevant in Patients with TP53-Mutated Myeloid Neoplasm Receiving Frontline Hypomethylating Agent Based Therapies. Lab Invest 2026; 106(3).
Document Type
Conference Proceeding
Publication Date
3-23-2026
Publication Title
Lab Invest
Keywords
venetoclax, aged, bone marrow tumor, cohort analysis, conference abstract, controlled study, diagnosis, drug therapy, female, gene frequency, human, karyotype, major clinical study, male, methylation, myeloproliferative neoplasm, overall survival, retrospective study, special situation for pharmacovigilance, WHO-5 Well-Being Index
Abstract
Disclosures: Richard Simon: None; Haipeng Shao: None; Emily Mason: None; Jingjing Zhang: None; Pranav Patwardhan: None; Nathanael Bailey: None; Amandeep Kaur: None; Payal Sojitra: None; Hamza Tariq: None; Megan Forrest: None; Sharmila Ghosh: None; Zenggang Pan: None; Caner Saygin: None; Peng Wang: None; Mark Roberts: None; Anamarija Perry: None; Girish Venkataraman: None Background: Myeloid Neoplasms (MN) with TP53 mutation (TP53MUT) represents a high-risk subgroup occurring in elderly patients who are often eligible only for hypomethylating agents (HMA)-based regimens with or without venetoclax. The interplay of blast counts and TP53 allelic state (single-hit TP53SH vs, multi-hit TP53MH) in this cohort is critical for accurate risk stratification and understanding outcomes Design: We examined 384 patients with TP53MUT MN and TP53 variant allele frequency ≥3% who received frontline HMA-based therapies with/without venetoclax. Patients with secondary disease arising from prior myeloproliferative neoplasm were excluded. We evaluated blast count (<20% [MDS] vs. ≥20% [AML]) and other clinicopathologic factors (including WHO5 TP53 allelic state). Primary outcome examined was 24-month overall survival (OS24) from diagnosis using Kaplan-Meir analysis and Cox modeling for estimating hazard ratio (HR). Results: Of 384 patients overall, 213 (56%) exhibited blasts ≥20% Those with AML were more likely to be older than 70 yrs (58% vs. 47% MDS group; P = .032) with MDS patients more likely to be female (63% vs. 51%; P = .014) and multi-hit TP53 allelic state (85% vs. 77% MDS group; P = .032). Proportions of patients with complex karyotype were comparable between MDS and AML subgroups. Examining co-alterations of genes other than TP53, patients with MDS and AML exhibited comparable frequencies of coalterations (P = .33). As expected, frontline use of venetoclax was significantly more frequent in AML patients (63% vs. 40% in MDS group; P < .0001). Looking at outcomes in entire cohort (1A), AML was associated with shorter median OS24 (7.7 mos. vs. 11.6 mos.; PLog-rank < .001) although, within venetoclax-treated patients, blast counts did not impact on OS24 (7.6 mos. vs. 8.1 mos.; PLog-rank = .21) Impact of blast count was more pronounced only in those with TP53SH allelic state (HR 2.4 [1.2–4.6]; P = .009; N = 70) (1B & 1C) Concurrent non-TP53 coalterations did not impact outcome (P = .46; N = 384). Looking at the interplay of blast counts and co-alterations, blast counts predicted adverse outcome only in those with co-alterations. (HR 1.9 [1.3–2.7]; P < .001; N = 206) without any impact in those without coalterations (1D). [Formula presented] [Formula presented] Conclusions: In this elderly cohort uniformly treated with HMA-based therapies, the WHO5 20% blast count threshold remains relevant for predicting inferior survival with impact restricted to those with TP53SH or concurrent coalterations.
Volume
106
Issue
3
