Two decades of targeted therapies in acute myeloid leukemia

Area of Science:

• Hematology
• Oncology
• Clinical Pharmacology

Background:

• Precision medicine is increasingly vital for treating acute myeloid leukemia (AML).
• A comprehensive review of targeted therapy trials is needed to guide future AML research.
• Understanding the clinical benefit and progression of targeted agents is crucial.

Purpose of the Study:

• To provide a complete overview of phase II and III trials for targeted therapies in AML over the past two decades.
• To assess the clinical benefit of targeted agents based on their progression from early to late-stage trials and FDA approval.
• To evaluate whether drugs were primarily developed for AML or repurposed.

Main Methods:

• Systematic review of phase II and III clinical trials investigating targeted therapies in AML between January 2000 and September 2020.
• Analysis of 167 agents targeting 96 distinct targets across 397 phase II trials.
• Assessment of drug progression, primary endpoints, and FDA approval status.

Main Results:

• 28 agents progressed to phase III trials, averaging three phase II trials each.
• Repurposed drugs showed less advancement in clinical development compared to AML-specific agents.
• Composite response was the most common primary endpoint in phase II trials.
• Of eight FDA-approved drugs, none included quality of life assessments, and three lacked overall survival benefit.

Conclusions:

• The return on investment for targeted therapy research in AML remains low for patients.
• Future AML trials should consider non-targeted agents and prioritize endpoints reflecting patient well-being.
• Current targeted therapies offer limited demonstrated clinical benefit and survival advantage for AML patients.