A Hopeful Leap Forward by Multicentric Cooperation for Precision-Based Therapy for Very Resistant, Relapsed, or...

Area of Science:

• Oncology
• Genomics
• Pediatric Hematology/Oncology

Background:

• Childhood leukemia often develops drug resistance.
• Genomic profiling offers potential for targeted therapies.
• Precision medicine approaches are emerging in pediatric oncology.

Purpose of the Study:

• To report results from a multicenter prospective clinical trial of the Leukemia Precision-based Therapy (LEAP) consortium.
• To evaluate the identification and validation of targetable genomic lesions and matching small-molecule agents in drug-resistant childhood leukemia.
• To assess the impact of genomic information on disease classification, treatment guidance, and translational research.

Main Methods:

• Multicentric prospective clinical trial.
• Identification of targetable genomic lesions in leukemia.
• Tiered evidence-based approach for genomic lesions and drug targets.
• Validation of small-molecule targeted agents.
• Treatment of individual patients based on genomic findings.

Main Results:

• Demonstrated the impact of genomic information on disease classification and treatment guidance.
• Showcased the utility of precision-based therapy in childhood leukemia.
• Highlighted challenges in target prediction for heterogeneous patient subgroups.
• Illustrated difficulties in clinical trial design for rare genetic alterations.

Conclusions:

• Genomic information is crucial for advancing leukemia treatment and translational research.
• Precision medicine in pediatric leukemia faces challenges in target identification and trial design for small, heterogeneous subgroups.
• Further research is needed to optimize precision therapy strategies for all children with leukemia.