Photo Credit: Syahrir Maulana
Research from ASH 2023 showed standard treatment options lack efficacy for patients with acute myeloid leukemia (AML) who are positive for the TP53 mutation.
Findings presented at the 65th ASH Annual Meeting showed that patients with AML who are positive for the TP53 mutation and receive common treatment options exhibited lower overall survival (OS) and complete remission rates.
According to a study published in the Journal of Hematology & Oncology that focused on the treatment outcomes of newly diagnosed, treatment-naïve patients with AML carrying TP53 mutations, TP53 mutations are found in 5% to 10% of patients with AML and are linked to treatment resistance and poor outcomes. The study analyzed three first-line therapies for TP53m AML: intensive chemotherapy, hypomethylating agents, and venetoclax combined with hypomethylating agents.
Based on 12 studies that met inclusion criteria, the results indicated that intensive chemotherapy had the highest complete remission rate at 43%. In contrast, venetoclax combined with hypomethylating agents and hypomethylating agents alone had complete remission rates of 33% and 13%, respectively. The authors noted that median OS was uniformly poor across treatments: intensive chemotherapy (6.5 months), venetoclax combined with hypomethylating agents (6.2 months), and hypomethylating agents (6.1 months).
Despite improved responses with intensive chemotherapy and venetoclax combined with hypomethylating, OS remained consistently low, emphasizing the urgent need for improved treatment options for newly diagnosed, treatment-naïve TP53 mutation-positive AML patients.
Optimal Treatment Remains Unclear
The study presented at ASH expanded on these findings and focused on a distinct subgroup of patients with AML characterized by the TP53 mutation associated with poor OS due to limited therapeutic options. According to the researchers, clinical trials may not adequately represent this subgroup because TP53-mutated patients are often older with comorbidities and prior treatments, making the optimal treatment unclear.
Real-world data (RWD) offers insights into demographics, clinical characteristics, and treatment outcomes in routine clinical practice. This retrospective observational study utilized the COTA real-world database to describe characteristics, first-line treatment patterns, and outcomes in TP53-mutated AML patients in the US.
The study included 884 adult patients with newly diagnosed AML and used next-generation sequencing (NGS) to analyze TP53 status. Researchers classified patients as TP53-positive (TP53+) or TP53-negative (TP53-). Testing for TP53 increased over time, with 75% diagnosed in 2018-2022. TP53+ patients were older, and the study team classified all participants as part of the European LeukemiaNet adverse risk group. Common treatment regimens included hypomethylating agent alone, hypomethylating agent with venetoclax, and intensive chemo with cytarabine. TP53+ patients were less likely to receive anti-leukemic treatment and had lower complete remission (CR) rates than TP53– patients. OS was shorter for TP53+ AML, irrespective of the treatment regimen. Patients treated with intensive chemo with cytarabine had longer OS, but they were generally younger and more fit than those receiving hypomethylating agent with venetoclax.
The study concluded that patients with TP53+ AML exhibit lower complete remission and OS rates across commonly used treatment regimens. It highlights the potential of RWD to characterize outcomes in specific genetic subtypes despite limited testing during the study period. However, the authors acknowledge limitations associated with observational data, including missing information and potential bias. The findings underscore the need for further research into novel treatments for TP53+ AML to improve patient outcomes.
