Survival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)

Abstract

We conducted a multi-center study to analyze factors predicting survival among patients with TP53mutated (m) AML receiving allogeneic hematopoietic stem cell transplant (allo-HSCT) in the recent era.Among 370 patients, 68 (18%) patients were bridge to allo-HSCT. The median age of the patients was 63 years (range, 33-75), 82% of patients had complex cytogenetics and 66% of patients had multi-hit TP53m. Forty three percent received myeloablative conditioning (MAC) and 57% received reduced intensity conditioning (RIC). The incidence of acute graft versus host disease (GVHD) was 37% and chronic GVHD was 44%. The median event-free survival (EFS) from the time of allo-HSCT was 12.4 months (95% CI: 6.24-18.55) and median overall survival (OS) was 24.5 months (95% CI: 21.80-27.25).In multivariate analysis utilizing variables that showed signi cance in univariate analysis, complete remission at day 100 post allo-HSCT retained signi cance for EFS (HR: 0.24, 95%

Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions

“…We note the enrichment of TP53 mutations in non‐Hispanic White patients, and racial disparities in therapeutic approaches are also worthy of consideration [27]. Further risk stratification using details of the TP53 genomic state in conjunction with morphologic assessment may guide tailored therapeutics and personalized treatment plans for this heterogeneous group [28–34].…”

Real World Predictors of Response and 24-month survival in high-grade TP53-mutated Myeloid Neoplasms

“…Likewise, among transplanted individuals, ongoing CR at day +100 post-alloSCT was significantly associated with better OS24 (62.7% vs. 36.8% for no CR; P fpm = .054), in congruence with the COMMAND study demonstrating significant beneficial impact of alloSCT in TP53 MUT MNs. 10 Early relapse by day+100 was significantly more likely in patients with an EPI6 signature present (P = .002), high EAp53 score (P = .018) with a marginal effect for CUX1 alterations (P = .08) at diagnosis. TP53 Risk Score (TP53RS) for TP53 MUT 4.3 mos.…”

Immunotherapy for Acute Myeloid Leukemia: Current Trends, Challenges, and Strategies

“…Trials of magrolimab + Aza ± Ven are also underway in high-risk AML subgroups with activity in both TP53wild-type and -mutant patients. Because of the historically poor outcomes of TP53-mutated AML to conventional chemotherapy [100][101][102], Ven-based regimens [103][104][105], and allo-HCT [106], magrolimab's efficacy in this molecular subgroup has drawn particular attention. Results of the TP53-mutated subgroup (n = 72) of the phase 1b study of magrolimab + Aza in AML showed a 43% CR/CRi/CRh/MLFS rate (of which 45% achieved MRD negativity) and 13% rate of subsequent HCT [18].…”