Clinical characteristics and overall survival among acute myeloid leukemia patients with TP53 gene mutation or chromosome 17p deletion

Abstract

Approximately 5% to 15% of acute myeloid leukemia (AML) patients have TP53 gene mutations (TP53m), which are associated with very poor outcomes. Adults (≥18 years) with a new AML diagnosis were included from a nationwide, de-identified, real-world database. Patients receiving first-line therapy were divided into three cohorts: venetoclax (VEN) + hypomethylating agents (HMAs; Cohort A), intensive chemotherapy (Cohort B), or HMA without VEN (Cohort C). A total of 370 newly diagnosed AML patients with TP53m (n = 124), chromosome 17p deletion (n = 166), or both (n = 80) were included. The median age was 72 years (range, 24–84); most were male (59%) and White (69%). Baseline bone marrow (BM) blasts were ≤30%, 31%–50%, and >50% in 41%, 24%, and 29% of patients in Cohorts A, B, and C, respectively. BM remission (<5% blasts) with first-line therapy was reported in 54% of patients (115/215) overall, and 67% (38/57), 62% (68/110), and 19% (9/48) for respective cohorts (median BM remission duration: 6.3, 6.9, and 5.4 months). Median overall survival (95% CI) was 7.4 months (6.0–8.8) for Cohort A, 9.4 months (7.2–10.4) for Cohort B, and 5.9 months (4.3–7.5) for Cohort C. There were no differences in survival by treatment type after adjusting for the effects of relevant covariates (Cohort A vs. C adjusted hazard ratio [aHR] = 0.9; 95% CI, 0.7–1.3; Cohort A vs. B aHR = 1.0; 95% CI, 0.7–1.5; and Cohort C vs. B aHR = 1.1; 95% CI, 0.8–1.6). Patients with TP53m AML have dismal outcomes with current therapies, demonstrating the high unmet need for improved treatments.