Current and future role of bispecific T-cell engagers in pediatric acute lymphoblastic leukemia

ABSTRACT

Introduction: The clinical application of immunotherapy has resulted into a significant improvement in the outcome of children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL). In this setting, the use of bispecific T-cell-engager antibodies (BiTEs), such as blinatumomab, which harness the cytotoxic activity of T cells against CD19-positive lymphoblasts, has emerged as a most promising and impactful strategy.

Areas covered: This review discusses the main structural and functional features of BiTEs, as well as the current status of their clinical application in childhood ALL. Moreover, future prospects to increase the efficacy of BiTEs are addressed.

Expert commentary: The promising results obtained in patients with advanced BCP-ALL pave the way for further improvement in the context of less resistant/advanced disease. Future research is rapidly progressing on several aspects, including the use of blinatumomab in first-line protocols, identification of factors predicting response, use of combinatorial approaches and bioengineering of new molecules with dual specificity or increased potency, stability and half-life. The results of these studies, expected to be available in the next future, will provide further advancement in the development of effective, impactful, targeted immunotherapy for treatment of childhood BCP-ALL, with the concrete potential to revolutionize the clinical practice.

KEYWORDS:

• Acute lymphoblastic leukemia
• immunotherapy
• bispecific T-cell engagers
• blinatumomab
• minimal residual disease
• relapsed
• refractory

Declaration of interest

F Locatelli is the responsible investigator for Italy of two Amgen-sponsored clinical trials using blinatumomab in pediatric patients. He has been a member of Amgen’s Scientific Advisory Boards for blinatumomab and received honoraria from Amgen as a Speaker. The other authors have no other relevant affiliations or financial involvement with any organization or entity or financial conflict with the subject matter or materials discussed in the manuscript to disclose.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.