Outcomes in patients with newly diagnosed TP53-mutated acute myeloid leukemia with or without venetoclax-based therapy

Background: Venetoclax (VEN) in combination with a hypomethylating agent (HMA) has become the standard of care for patients aged >75 years and for those not eligible for intensive chemotherapy who have newly diagnosed acute myeloid leukemia (AML). The benefit of VEN-based therapy in patients who have newly diagnosed AML with mutations in the TP53 gene (TP53^mut) over standard therapy is undefined. Methods: In this single-institutional, retrospective analysis, the authors assessed the clinical outcomes of 238 patients with newly diagnosed TP53^mut AML and compared the clinical characteristics, response to different therapies, and outcomes of those who received VEN-based (n = 58) and non–VEN-based (n = 180) regimens. Results: Patients who received VEN-based regimens were older (aged >65 years: 81% vs 65%; P =.02) and had higher response rates (complete remission, 43% vs 32%; P =.06) than those who received non–VEN-based regimens. Compared with patients who received non–VEN-based regimens, no difference in overall survival (median, 6.6 vs 5.7 months; P =.4) or relapse-free survival (median, 4.7 vs 3.5 months; P =.43) was observed in those who received VEN-based regimens, regardless of age or intensity of treatment. Conclusions: The addition of VEN to standard treatment regimens did not improve outcomes in younger or older patients who had TP53^mut AML. These data highlight the need for novel therapies beyond VEN to improve the outcome of patients with TP53^mut AML.