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Multicenter trials in children and young adults using second-generation CD19-targeted chimeric antigen receptor (CAR) T cells have shown dramatic levels of remission in patients with multiply relapsed/refractory disease (80% to ≥90%). Early results in adult trials have also shown significant responses, and strategies aimed at mitigating toxicities associated with the therapy have improved tolerability. Therefore, if available, CAR T-cell therapy deserves consideration for salvage of children and adults with B-lineage acute lymphoblastic leukemia (B-ALL) who are multiply relapsed, refractory, or relapsed after a previous allogeneic transplantation. For patients with a first relapse or who have persistent minimal residual disease (MRD) after initial or relapse therapy, treatment with blinatumomab or inotuzumab is reasonable to help patients achieve MRD remission before definitive therapy with allogeneic hematopoietic cell transplantation (HCT). A number of studies in younger patients using 4-1BB-based CAR T-cell constructs lentivirally transduced into patient T cells and then optimally expanded have resulted in long-term persistence without further therapy. In 1 study using CD28-based CARs in adults, the benefit of HCT after CAR T-cell therapy was not clear, because a group of patients experienced long-term remissions without HCT. These data suggest that CAR T-cell therapy may be able to substitute for transplantation in many patients, avoiding the risks and long-term consequences of HCT. With this is mind, and with emerging data better defining ways of enhancing CAR T-cell persistence and avoiding relapse through antigen escape, CAR T cells will have a growing role in treatment of both pediatric and adult B-ALLs in the coming years.
PMID: 30504287 [PubMed - in process]