Targeted therapies in pediatric B-Cell acute lymphoblastic leukemia: mechanisms, efficacy, and future directions

TL;DR

This review explores how targeted therapies are improving treatment for pediatric B-cell acute lymphoblastic leukemia, offering better outcomes with fewer side effects.

Contribution

The paper provides a comprehensive analysis of targeted therapies for pediatric B-cell ALL, highlighting their mechanisms and clinical efficacy.

Findings

Targeted therapies improved progression-free survival and overall response rates in relapsed/refractory ALL patients.

CD19-directed CAR-T-cell therapy and bispecific antibodies like blinatumomab showed high remission rates in early trials.

BCR-ABL1-positive ALL patients benefited from tyrosine kinase inhibitors combined with chemotherapy.

Abstract

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children and is characterized by rapid progression and, in some cases, a high risk of relapse. Targeted therapies have revolutionized treatment with greater specificity, reduced systemic toxicity and a better prognosis.

This review provides a comprehensive analysis of current targeted therapies for pediatric B-cell ALL, focusing on their mechanisms of action, efficacy, safety profiles, advantages, and remaining challenges.

A systematic review of clinical trials published over the past 15 years was conducted. The analyzed therapies include monoclonal antibodies, antibody‒drug conjugates, tyrosine kinase inhibitors, proteasome inhibitors, and chimeric antigen–receptor T-cell (CAR-T cell) immunotherapy.

Targeted therapies improved progression-free survival and overall response rates, particularly in patients with relapsed/refractory ALL. CD19-directed CAR-T-cell therapy and bispecific antibodies (e.g., blinatumomab) have demonstrated high remission rates in early-phase clinical trials. Additionally, BCR-ABL1-positive ALL patients show benefit from tyrosine kinase inhibitors when combined with chemotherapy.

Targeted therapies represent a paradigm shift in ALL treatments, enabling more personalized and effective strategies. Their integration into standard protocols, especially for high-risk and relapsed patients, is crucial to enhancing long-term outcomes.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251110522, identifier CRD420251110522

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