Poor Survival Across Treatments for TP53-Mutated AML

By Cecilia Brown - Last Updated: April 27, 2023

Survival was “uniformly poor” across all therapies in patients with treatment-naïve TP53-mutated acute myeloid leukemia (AML), according to a recent analysis.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center and colleagues conducted the systematic review and meta-analysis to describe and compare treatment outcomes in treatment-naïve patients with newly diagnosed TP53-mutated AML.

The analysis included randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies of patients with TP53-mutated AML who received first-line treatment with intensive chemotherapy, hypomethylating agents (HMAs), or venetoclax combined with HMAs.

All included studies reported on complete remission (CR), CR with incomplete hematologic recovery, overall survival (OS), event-free survival (EFS), duration of response, and overall response rate (ORR).

Dr. Daver and colleagues identified 3,006 abstracts and 17 publications describing 12 studies that met the inclusion criteria by searching the EMBASE and MEDLINE databases. They used random-effects models to pool response rates, and they analyzed time-related outcomes with the medians of medians method.

They found that intensive chemotherapy was associated with the highest CR rate (43%), followed by venetoclax plus HMAs (33%), and HMAs (13%).

However, rates of CR/CR with incomplete hematologic recovery were comparable between intensive chemotherapy (46%) and venetoclax plus HMAs (49%). The rate of CR/CR with incomplete hematologic recovery was 13% for HMAs.

The median OS was 6.5 months with intensive chemotherapy, while it was 6.2 months with venetoclax plus hypomethylating agents, and was 6.1 months with HMAs.

The median OS was “uniformly poor across treatments,” Dr. Daver and colleagues wrote.

The ORR was highest with venetoclax plus HMAs (65%), while it was 47% with HMAs alone, and was 41% with intensive chemotherapy.

The estimated EFS was 3.7 months for intensive chemotherapy, but was not reported for venetoclax plus HMAs or HMAs alone, according to the study’s authors.

The duration of response was longest with venetoclax plus HMAs (five months), while it was 3.5 months with intensive chemotherapy. The duration of response was not reported for HMAs.

“Despite improved responses seen with [intensive chemotherapy] and [venetoclax plus] HMAs compared to HMAs, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53[-mutated] AML, demonstrating a significant need for improved treatment for this difficult-to-treat population,” Dr. Daver and colleagues concluded.


Daver NG, Iqbal S, Renard C, et al. Treatment outcomes for newly diagnosed, treatment-naïve TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis. J Hematol Oncol. 2023;16(1):19. doi:10.1186/s13045-023-01417-5

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