Feuchtinger Tobias, Bader Peter, Subklewe Marion, Breidenbach Maike, Willier Semjon, Metzler Markus, Gökbuget Nicola, Hauer Julia, Müller Fabian, Schlegel Paul-Gerhardt, Frühwald Michael, Schmid Christoph, Troeger Anja, Baldus Claudia, Meisel Roland, Künkele Annette, Topp Max, Bourquin Jean-Pierre, Cario Gunnar, Von Stackelberg Arend, Peters Christina
Department of Paediatric Haematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Germany; Bavarian Cancer Research Center (BZKF), R/R ALL Study Group; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg.
Goethe University, University Hospital, Department for Children and Adolescents, Division for Stern Cell Transplantation, Immunology and Intensive Care, Frankfurt.
Haematologica. 2024 Dec 1;109(12):3892-3903. doi: 10.3324/haematol.2023.283780.
The ongoing development of immunotherapies, including chimeric antigen receptor (CAR) T cells, has revolutionized cancer treatment. In pediatric relapsed/refractory B-lineage acute leukemia antiCD19-CAR induce impressive initial response rates, with event-free survival plateauing at 30-50% according to long-term follow-up data. During the interval between diagnosis of relapse or refractoriness and CAR T-cell infusion, patients require a bridging therapy. To date, this therapy has consisted of highly variable approaches based on local experience. Here, in an European collaborative effort of pediatric and adult hematologists, we summarize current knowledge with the aim of establishing guidance for bridging therapy. We discuss treatment strategies for different subgroups of patients, the advantages and disadvantages of low- and high-intensity regimens, and the potential impact of bridging therapy on outcomes after CAR T-cell infusion. This guidance is a step towards cross-institutional harmonization of bridging therapy, including personalized approaches. This will allow better comparability of clinical data and increase the level of evidence for the treatment of children and young adults with relapsed/ refractory B-lineage acute leukemia until they can receive CAR T-cell infusion.
包括嵌合抗原受体（CAR）T细胞在内的免疫疗法的不断发展，彻底改变了癌症治疗方式。在儿童复发/难治性B系急性白血病中，抗CD19-CAR诱导出令人印象深刻的初始缓解率，根据长期随访数据，无事件生存率稳定在30%-50%。在复发或难治性诊断与CAR T细胞输注之间的间隔期，患者需要一种桥接治疗。迄今为止，这种治疗方法因地区经验不同而差异很大。在此，在欧洲儿科和成人血液学家的合作努力下，我们总结了当前的知识，旨在为桥接治疗建立指导原则。我们讨论了不同患者亚组的治疗策略、低强度和高强度方案的优缺点，以及桥接治疗对CAR T细胞输注后疗效的潜在影响。该指导原则是朝着桥接治疗的跨机构协调迈出的一步，包括个性化方法。这将使临床数据具有更好的可比性，并提高治疗复发/难治性B系急性白血病儿童和青年患者直至他们能够接受CAR T细胞输注的证据水平。
