(027) Characterization of Treatment Outcomes with Secondary Induction Regimens in TP53-Mutated Newly Diagnosed Acute Myeloid Leukemia Patients

Poster Abstract:

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by a clonal expansion of myeloid hematopoiesis. Management depends on performance status, age, and risk stratification based on mutational status. Treatment outcomes largely depend on risk stratification based on mutational status with three overall risk categories: favorable, intermediate, or poor. TP53 mutations, reported in 5-15% of all AML cases, are associated with unfavorable risk and adverse outcomes. In general, standard curative treatment for AML consists of intensive induction chemotherapy (cytarabine and idarubicin/daunorubicin) followed by consolidation chemotherapy, allogeneic stem-cell transplantation, or both. TP53-mutated AML malignancies have poor response rates to conventional cytarabine-based chemotherapy regimens with response rates of 20-30%. Median survival is four to six months and overall survival (OS) is approximately ten months after allogeneic stem cell transplantation. Therefore, treatment of patients with TP53-mutated AML remains a challenge. Recent data has shown promising results in terms of complete response (CR) and variable OS with hypomethylating agents, either as monotherapy or in combination with venetoclax in TP53-mutated AML. Current literature highlights the unmet need for new therapies that can effectively treat newly diagnosed, treatment-naïve TP53-mutated AML and improve real-world outcomes of secondary induction regimens.

Objective: The purpose of this study is to describe the treatment outcomes of subsequent induction regimens in terms of CR and/or CR with incomplete hematologic recovery (CRi) in newly diagnosed TP53-mutated AML patients.

Methods: This is a single-center, retrospective, descriptive, cohort study that includes data collected from the electronic medical records (EMRs) of adult patients with TP53-mutated AML who have received induction chemotherapy at a hospital within the Houston Methodist System between June 1, 2016 and June 1, 2023. Patients will be excluded if they had concurrent malignancies (other than AML) requiring active therapy, received any other investigational agents, had acute promyelocytic leukemia with PML-RARA or t(15;17), or were transferred to another institution that does not share EMRs with Houston Methodist. Primary objective includes assessment of response rates to secondary induction regimens in terms of CR and CRi. Secondary objectives include response rates to primary induction regimens, percentage of event free survival at 6 months, OS, and duration of response for patients who achieved CR or CRi.

Results: Data collection and analysis are ongoing. Finalized results will be presented at HOPA.

Conclusion: This study aims to add to the body of literature reviewing treatment outcomes of TP53-mutated AML and response rates of secondary induction chemotherapy regimens.

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