The Use of Targeted Therapy in Pediatric Acute Lymphoblastic Leukemia: Exploring Novel Approaches and Emerging Therapies.
This review summarizes available pediatric ALL efficacy and toxicity evidence for targeted and immune-based therapies, including blinatumomab, inotuzumab ozogamicin, and tisagenlecleucel, and advocates evaluating their earlier integration into frontline treatment.
Open original publication →What the AI sees
This review summarizes available pediatric ALL efficacy and toxicity evidence for targeted and immune-based therapies, including blinatumomab, inotuzumab ozogamicin, and tisagenlecleucel, and advocates evaluating their earlier integration into frontline treatment.
Research significance
The record indicates that targeted therapies have clinical roles in relapsed or refractory pediatric ALL; the authors infer that incorporating selected agents into frontline therapy for high-risk patients could improve responses and remission duration while reducing reliance on toxic chemotherapy, but this prospective benefit is not established by the supplied record.
Source abstract
With modern risk stratification of multi-agent cytotoxic chemotherapy protocols, we now cure the majority of patients with pediatric acute lymphoblastic leukemia (ALL). However, patients with high-risk features or relapsed disease continue to have suboptimal outcomes. Conventional chemotherapy agents may increase long term organ toxicities even in more favorable patients. Improved understanding of the molecular characteristics of pediatric ALL has led to the preclinical and clinical development of more targeted and less systemically toxic therapeutic options for patients with ALL. Agents such as blinatumomab, inotuzumab ozogamicin, tisagenlecleucel and several others have revolutionized the treatment of relapsed or refractory ALL by either directing therapies locally to leukemic cells or by targeting specific leukemogenic pathways. Here we present current evidence for efficacy and toxicity profiles for these targeted therapies in pediatric patients with ALL. Many of these strategies have been more comprehensively studied in the adult population and we will highlight ongoing and needed clinical trials in pediatrics. We need to overcome our historically delayed approach to introducing new therapeutic options in pediatrics, as adults often benefit from innovations for years before they are evaluated in children. More proactively incorporating these emerging treatments into frontline therapy for the most vulnerable, high-risk pediatric ALL populations could meaningfully reshape our treatment paradigm. Earlier collaboration for development of clinical trials across pediatric and adult ALL may facilitate more rapid access to promising agents. We anticipate that successful upfront integration of more targeted approaches will improve response rates, reduce reliance on highly toxic chemotherapies and ultimately increase the likelihood of duration of remission. We expect the next generation of clinical trials will credential more targeted therapies for use in frontline therapy with the goal of improved outcomes with minimized toxicity for all patients with pediatric ALL, not just those with more favorable disease characteristics.