Novel therapy for childhood acute lymphoblastic leukemia

ABSTRACT

Introduction: During recent decades, the prognosis of childhood acute lymphoblastic leukemia (ALL) has improved dramatically, nowadays, reaching a cure rate of almost 90%. These results are due to a better management and combination of old therapies, refined risk-group stratification and emergence of minimal residual disease (MRD) combined with treatment’s intensification for high-risk subgroups. However, the subgroup of patients with refractory/relapsed ALL still presents a dismal prognosis indicating necessity for innovative therapeutic approaches.

Areas covered: We performed an exhaustive review of current first-line therapies for childhood ALL in the worldwide main consortia, summarized the major advances for front-line and relapse treatment and highlighted recent and promising innovative therapies with an overview of the most promising ongoing clinical trials.

Expert opinion: Two major avenues marked the beginning of 21^st century. First, is the introduction of tyrosine-kinase inhibitor coupled to chemotherapy for treatment of Philadelphia positive ALL opening new treatment possibilities for the recently identified subgroup of Ph-like ALL. Second, is the breakthrough of immunotherapy, notably CAR T-cell and specific antibody-based therapy, with remarkable success observed in initial studies.

This review gives an insight on current knowledge in these innovative therapeutic directions, summarizes currently ongoing clinical trials and addresses challenges these approaches are faced with.

KEYWORDS:

• Acute lymphoblastic leukemia
• childhood
• chimeric antigen receptor (CAR) T-cells
• immunotherapy
• Ph-like ALL
• risk stratification
• tyrosine-kinase inhibitor

Article highlights

• Despite a major improvement in the curability of childhood acute lymphoblastic leukemia (childhood-ALL), the subgroup of refractory/relapsed childhood ALL is still associated with a dismal prognosis

• Better characterization of childhood-ALL, refined risk-groups stratification and widespread assessment of minimal residual disease were major advances

• The impressive success of tyrosine-kinase inhibitor for Philadelphia positive ALL marked the entry in the era of precision medicine for ALL

• A new subgroup of high-risk ALL, Ph-like ALL, is a promising model for effective targeted therapy

• The recent remarkable results of immunotherapy in ALL offer promising therapeutic avenues for otherwise incurable cases of ALL

• The new challenge is to foresee how these therapies could be combined to optimize the treatment and improve the outcome of childhood ALL

This box summarizes key points contained in the article.

Acknowledgement

We are thankful to Guylaine Ruel for designing the figure.

This review is related to the authors research grants funded by Foundation Charles Bruneau and PSVT2 of MEIE.

Declaration of interest

H. Bittencourt is consulting for Jazz Pharmaceuticals. 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

This paper was not funded