McCall David, Catueno Samanta, Ramakrishnan Ramya, Tewari Priti, Sheikh Irtiza, Gibson Amber, Nuñez Cesar A, Garcia Miriam B, Cuglievan Branko
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Pediatric Stem Cell Transplantation and Cell Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Acta Haematol. 2025 May 5:1-16. doi: 10.1159/000546249.
The integration of novel antibody-mediated targeted therapies into both relapsed/refractory (R/R) and frontline pediatric acute lymphoblastic leukemia (ALL) treatment protocols has led to critical advancements in the field. Current research efforts focus on optimizing targeted therapies to enhance precision and efficacy while minimizing toxicity by reducing chemotherapy. A notable example is the addition of blinatumomab, demonstrating superiority over conventional chemotherapy, with an 8% increase in disease-free survival at an interim analysis, reaching 96%. Inotuzumab ozogamicin (InO) has also shown promise, achieving nearly a 70% complete response rate in pediatric R/R B-cell ALL (B-ALL) trials. Additionally, daratumumab in T-cell ALL (T-ALL) and chimeric antigen receptor T-cell therapies, particularly CD19-directed (B-ALL) and CD7-directed (T-ALL) strategies, are under active investigation.
This review will provide an overview of targeted antibody-mediated immunotherapies in both B-ALL and T-ALL, with a focus on their pediatric applications, supporting data, and future prospects.
The next cycle of frontline trials in pediatric ALL will incorporate more immunotherapy with reduction of chemotherapy. Subsequent trials will utilize more concurrent chemoimmunotherapy blocks as precision testing and risk-adapted therapy will continue to develop. These advancements reflect a paradigm shift toward more precise, less toxic treatment strategies in pediatric ALL.
将新型抗体介导的靶向治疗整合到复发/难治性（R/R）和一线儿科急性淋巴细胞白血病（ALL）治疗方案中，已推动了该领域的重大进展。当前的研究工作集中在优化靶向治疗，以提高精准度和疗效，同时通过减少化疗来降低毒性。一个显著的例子是添加了博纳吐单抗，其显示出优于传统化疗的效果，在中期分析中无病生存率提高了8%，达到96%。奥英妥珠单抗（InO）也显示出前景，在儿科R/R B细胞急性淋巴细胞白血病（B-ALL）试验中实现了近70%的完全缓解率。此外，达雷妥尤单抗在T细胞急性淋巴细胞白血病（T-ALL）以及嵌合抗原受体T细胞疗法，特别是CD19导向（B-ALL）和CD7导向（T-ALL）策略方面，正在积极研究中。
本综述将概述B-ALL和T-ALL中靶向抗体介导的免疫疗法，重点关注其儿科应用、支持数据和未来前景。
儿科ALL的下一轮一线试验将纳入更多免疫疗法并减少化疗。后续试验将采用更多同步化疗免疫疗法模块，因为精准测试和风险适应性治疗将继续发展。这些进展反映了儿科ALL治疗策略向更精准、毒性更小的模式转变。
