Blinatumomab in pediatric acute lymphoblastic leukemia: current and future use.

Treatment outcomes for pediatric acute lymphoblastic leukemia (ALL) have improved considerably, with overall survival rates in high-income countries now exceeding 90% as a result of the introduction of risk-adapted chemotherapy and improved supportive care. Further improvement in the outcome of ALL requires new approaches, such as immunotherapy. Blinatumomab, a bispecific antibody to CD3 and CD19, is approved by the U.S. Food and Drug Administration for use in the consolidation phase of multi-agent chemotherapy for B-ALL in adults and children (aged ≥1 month). Randomized studies in pediatric patients with B-ALL in the relapsed/refractory and frontline settings have shown that blinatumomab, when added to chemotherapy or used to replace intensive chemotherapy, results in better outcomes and fewer adverse effects than are observed with conventional chemotherapy alone. Resistance to blinatumomab is associated with high ALL burden, CD19 loss/downregulation, and T-cell dysfunction, and its efficacy against extramedullary disease, especially in the central nervous system, is limited. In addition, the serum half-life of blinatumomab is short, necessitating continuous intravenous infusion, and it can cause distinct adverse effects such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and hypogammaglobulinemia. Therefore, medical staff require training in administering blinatumomab and monitoring its adverse effects. The development of subcutaneous administration of blinatumomab will make its delivery easier. Whether it is feasible to reduce or eliminate conventional chemotherapy by combining blinatumomab, other forms of immunotherapy, and molecular targeting therapy to improve outcomes while reducing adverse effects requires further evaluation in the frontline setting. Furthermore, longitudinal monitoring is necessary to evaluate the as-yet-unknown long-term adverse effects. Lastly, the experience obtained with blinatumomab in high-income countries should be expanded to low-/middle-income countries, where most of the global population reside and where the outcomes of ALL are suboptimal.