Immunotherapy in Pediatric B-Cell Acute Lymphoblastic Leukemia: Advances and Ongoing Challenges
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REVIEW ARTICLE
Immunotherapy in Pediatric B‑Cell Acute Lymphoblastic Leukemia: Advances and Ongoing Challenges Sylwia Jasinski1 · Francis Andrew De Los Reyes2 · Gloria Contreras Yametti1 · Joanna Pierro1 · Elizabeth Raetz1 · William L. Carroll1
© Springer Nature Switzerland AG 2020
Abstract Leukemia, most commonly B-cell acute lymphoblastic leukemia (B-ALL), accounts for about 30% of childhood cancer diagnoses. While there have been dramatic improvements in childhood ALL outcomes, certain subgroups—particularly those who relapse—fare poorly. In addition, cure is associated with significant short- and long-term side effects. Given these challenges, there is great interest in novel, targeted approaches to therapy. A number of new immunotherapeutic agents have proven to be efficacious in relapsed or refractory disease and are now being investigated in frontline treatment regimens. Blinatumomab (a bispecific T-cell engager that targets cluster of differentiation [CD]-19) and inotuzumab ozogamicin (a humanized antibody–drug conjugate to CD22) have shown the most promise. Chimeric antigen receptor T (CAR-T) cells, a form of adoptive immunotherapy, rely on the transfer of genetically modified effector T cells that have the potential to persist in vivo for years, providing ongoing long-term disease control. In this article, we discuss the clinical biology and treatment of B-ALL with an emphasis on the role of immunotherapy in overcoming the challenges of conventional cytotoxic therapy. As immunotherapy continues to move into the frontline of pediatric B-ALL therapy, we also discuss strategies to address unique side effects associated with these agents and efforts to overcome mechanisms of resistance to immunotherapy.
1 Introduction Leukemia, the most common childhood malignancy, accounts for about 30% of childhood cancer diagnoses [1]. More than three-quarters of cases are acute lymphoblastic leukemia (ALL), with 85% of those being B-cell ALL (B-ALL) and the remainder T-cell ALL and other rare subtypes. There have been dramatic improvements in childhood ALL outcomes over the past five decades, with 90% of children surviving ≥ 5 years from initial diagnosis [2]. Despite these advances, the burden of therapy for the children who are cured is substantial, with both short- and long-term toxicities, and some subgroups do not fare well, such as infants, adolescents, young adults, and those with unfavorable * William L. Carroll [email protected] 1
2
Perlmutter Cancer Center, Smilow 1211, Division of Pediatric Hematology/Oncology, Department of Pediatrics, NYU Langone Health, 560 First Avenue, New York, NY 10016, USA Department of Pharmacy, NYU Langone Health, New York, NY, USA
Key Points Although the overall prognosis for childhood acute lymphoblastic leukemia (ALL) is excellent, it remains a leading cause of morbidity and mortality in pediatric cancer, especially in certain subgroups of patients such as infants, adolescents, young adults, and those with unfavorable genomic alterations. The use of targ
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