First-Line Treatment Outcomes in TP53-Mutated Acute Myeloid Leukemia: A

Systematic Review and Meta-Analysis

Ali H. Mohamedi1, Khaled Al Bakri2, Anika Patel1, Ashwin Sunderraj1, Abril Carrillo1, Huda Baidoun3, Julia Anderson2, Alejandro Marino Velarde2, Vivian Irizarry-Gatell2, Robert Collins2

 

Stephen Chung2, Amir Toor Clayton Jackson2, Yazan Madanat2

1. Department of Internal Medicine, UT Southwestern, Dallas, TX; 2. Department of Internal Medicine – Hematology Oncology, UT Southwestern, Dallas, TX; 3. University of Jordan, Amman,Jordan

Background

• TP53m AML is an adverse-risk subtype

with treatment resistance, frequent relapse,

and poor survival.

• Frontline approaches include IC, LIT, and

HMA ± VEN.

AIMS

• The optimal frontline strategy remains

uncertain due to variable response and

survival outcomes.

• Evaluate the efficacy of frontline treatment

strategies in TP53-mutated AML by

comparing response to different therapies

• Assess whether improved treatment

responses translate into meaningful

survival benefit

Conclusions

 IC and HMA+VEN achieved higher CR

rates, with IC also producing higher CR/CRi

than LIT.

• More patients proceeded to HCT with IC

than LIT (30% vs 9%; P=0.007).

• Despite improved responses, median OS

remained ~6 months, highlighting the need

for rapid disease control and early HCT in

eligible patients.

Discussion

 Persistent TP53m clones may contribute

to treatment resistance and relapse

• Allo-HCT remains the principal potentially

curative strategy

• Substantial study heterogeneity limit direct

treatment comparisons, highlighting the need

for therapies capable of achieving deeper

TP53 clonal clearance and durable disease

control.

Selected References

• DiNardo CD, et al. Azacitidine and venetoclax in previously untreated acute myeloid

leukemia. N Engl J Med. 2020;383:617–629.

• Pollyea DA, et al. Outcomes in patients with poor-risk cytogenetics with or without TP53

mutations treated with venetoclax and azacitidine. Clin Cancer Res. 2022;28:5272–5279.

• Daver NG, et al. TP53-mutated myelodysplastic syndrome and acute myeloid leukemia:

biology, current therapy, and future directions. Cancer Discov. 2022;12:2516–2529.

*Full reference list will be available in manuscript*