Approaches for bridging therapy prior to chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic B-lineage leukemia in children and young adults

Abstract

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.