MDS-372: TP53 Mutated del(5q) Myelodysplastic Syndromes (MDS) Patients Have Survivals Comparable to Those with TP53 Wild-Type

Abstract

Background: TP53 mutations confer dismal prognosis in many hematologic malignancies, including MDS in general. It is frequently found in higher-risk/therapy-related MDS. However, 15-20% can occur in patients with del(5q), a subgroup that is known to have a more favorable risk. A prior study suggests TP53 mutations are associated with worse outcomes in del(5q) MDS. Objective: To assess the prognostic impact of TP53 mutations in del(5q) MDS patients and to report response to lenalidomide. Methods: This is a retrospective study of del(5q) MDS patients who were treated at the Moffitt Cancer Center from 2001 to 2019. Out of 132 patients identified, 63 had molecular data available and represent the cohort of present study. Univariate (log-rank), multivariate (Cox regression), and Kaplan-Meier (log-rank) analyses were performed. Results: Of the 63 patients (26M/37F), 23.8% were found to have TP53 mutation. Majority had isolated del(5q) (85%) with the remaining del(5q) plus other aberration(s) but not meeting criteria as complex. A total of 43 patients (68.3%) received lenalidomide (73.3% TP53 MT and 66.7% TP53 WT, p=NS) with 37.2%, 55.8%, and 7% achieving HI, NR, and DP/death, respectively. AML transformation occurred in 14.3% (20% TP53 MT and 12.5% TP53 WT, p=NS). Other common mutations include TET2 (19%), DNMT3A (17%), and SF3B1 (10%). The median OS was 76.6 months (median follow-up: 71.3 months). There was no significant difference in OS regardless of TP53 mutational status (p=0.72). Among patients who received lenalidomide, mOS for HI, NR, and DP/death were 142.2, 66, and 25.6 months, respectively (p ≤ 0.001). Univariate analysis showed lenalidomide response significantly impacted OS (HI:HR 0.02, 95% CI: 0.00-0.11, p ≤ 0.001; NR:HR 0.08, 95% CI: 0.02-0.43, p=0.003). Multivariate regression using covariates including TP53 status confirmed lenalidomide response to be independently associated with outcomes. Conclusions: There was no significant difference in OS in patients with TP53 MT vs. TP53 WT. A substantial portion of del(5q) MDS patients benefited from lenalidomide. Despite the known overall adverse association between TP53 and MDS, our data suggests the del(5q) subset behaves differently, which adds to the heterogeneity of the disease. Further studies are needed to clarify the impact of treatments and somatic mutations on outcomes.