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Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia

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Optimizing outcomes in secondary AML.

Andrew Matthews¹, Keith W Pratz¹

¹Abramson Cancer Center, Hospital of University of Pennsylvania, Philadelphia, PA.

Hematology. American Society of Hematology. Education Program

|December 9, 2022

Summary

Secondary acute myeloid leukemia (AML) has poor outcomes. While novel therapies show promise, TP53 mutations remain a challenge, and allogeneic transplant outcomes are limited by molecular features.

Area of Science:

Hematology
Oncology
Cancer Therapeutics

Background:

Secondary acute myeloid leukemia (AML) arises from prior hematologic disorders or cancer treatments, often presenting with inferior prognoses.
Standard cytarabine chemotherapy has shown limited efficacy for decades.
Emerging therapies like liposomal cytarabine/daunorubicin and venetoclax offer improved outcomes but face challenges.

Purpose of the Study:

To review the current landscape of secondary AML treatment.
To highlight unmet needs, particularly concerning TP53 mutations.
To discuss the role of novel agents and allogeneic transplantation.

Main Methods:

Review of current literature and clinical trial data for secondary AML.
Analysis of outcomes associated with conventional chemotherapy, novel therapies, and allogeneic transplantation.

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Evaluation of the impact of specific molecular mutations, such as TP53, on treatment response.

Main Results:

Novel therapies demonstrate improved outcomes compared to standard care.
TP53 mutations are linked to poor responses to current novel therapies.
Allogeneic transplant is curative but outcomes are negatively impacted by pre-transplant molecular risk factors.

Conclusions:

Despite advances, secondary AML, especially with TP53 mutations, remains an area of unmet clinical need.
Immune-targeted therapies show early promise but require further validation.
Optimal treatment strategies for secondary AML are still under investigation, with allogeneic transplant offering the best curative potential but requiring risk stratification.