KTE-X19 efficacious in adults with B-ALL

Abstract

0123456789();: Nature reviews | CliniCal OnCOlOgy ... the efficacy of KTE-X19 in this group is striking ... Anti-CD19 chimeric antigen receptor (CAR) T cell therapy is an approved treat ment modality for children and young adults (aged 3–25 years) with relapsed and/or refractory B cell acute lymphoblastic leukaemia (R/R B-ALL). Now, data from the ZUMA-3 trial demonstrate that the efficacy of such therapy extends to older adults with this disease. ZUMA-3 is a pivotal phase II trial of the autologous CD19-targeted CAR T cell product brexucabtagene autoleucel (KTE-X19) in patients ≥18 years of age (median 40 years; 15% ≥65 years) with R/R B-ALL. KTE-X19 was manufactured success fully for 65 (92%) of 71 patients enrolled. Ultimately, 55 patients (77%) received a single KTE-X19 infusion, and 39 (71%) had complete remission with (56%) or without (15%) complete haematological recovery, meeting the primary end point of the trial. Among the 39 responders, 38 achieved minimal residual disease negativity and the median duration of remission (mDoR) was 12.8 months. The median relapse-free survival (mRFS) duration was 11.6 months in all treated patients and 14.2 months in responders; median overall survival (mOS) was 18.2 months and not reached, respectively (after a median follow-up duration of 16.4 months). Notably, the mDoR and mRFS were not affected upon censoring for consolidative allogeneic stem cell transplantation (allo-SCT) in 10 patients. Most patients (89%) had cytokine-release syndrome, which was of grade 3 or 4 in 24%. Grade ≥3 neurological events occurred in 25% of patients, including one case of fatal brain herniation. A death from septic shock was also attributed to study treatment. Despite the approval of novel treatments such as blinatumomab and inotuzumab ozogamicin, adults with R/R B-ALL typically have an mOS of <8 months, which is largely dependent on allo-SCT consolidation. Therefore, the efficacy of KTE-X19 in this group is striking, and is similar to that of the CAR T cell product indicated for paediatric patients. Thus, approval of KTE-X19 for adults with R/R B-ALL is anticipated.