New targeted therapies for relapsed pediatric acute lymphoblastic leukemia

ABSTRACT

Introduction: The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Likewise, early experiences with new immunotherapeutic approaches have shown great promise.

Areas covered: We performed a literature search on PubMed and recent meeting abstracts using the keywords below. We focused on the biology and clonal evolution of relapsed disease highlighting potential new targets of therapy. We further summarized the results of early trials of the three most prominent immunotherapy agents currently under investigation.

Expert commentary: Discovery of targetable pathways that lead to drug resistance and recent breakthroughs in immunotherapy show great promise towards treating this aggressive disease. The best way to treat relapse, however, is to prevent it which makes incorporation of these new approaches into frontline therapy the best approach. Challenges remain to balance efficacy with toxicity and to prevent the emergence of resistant subclones which is why combining these newer agents with conventional chemotherapy will likely become standard of care.

KEYWORDS:

• Acute lymphoblastic leukemia
• relapse
• clonal evolution
• targeted therapy
• immunotherapy
• chimeric antigen receptor T-cells
• bispecific T-cell engagers
• monoclonal antibodies

Acknowledgments

The authors would like to acknowledge support from the following agencies: National Cancer Institute National Institute of Health (R01 CA140729-05, WLC and TB), the Leukemia and Lymphoma Society Specialized Center for Research (SCOR, WLC), the Perlmutter Cancer Center (P30 CA016087) and the Three Strohm Sister’s Foundation (LH).

Declaration of interest

WL Carroll chairs a safety and monitoring board for Amgen, the pharmaceutical company who manufactures blinatumomab. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

No funding to declare.