Sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt Lymphoma.

Single antigen-targeted chimeric antigen receptor (CAR) T-cell therapy may be insufficient to induce a durable response in pediatric aggressive B-cell lymphomas. The clinical trial (ChiCTR1800014457) examined the feasibility of sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Twenty-three patients received the first CD19 CAR T-cell infusion. The patients who did not achieve an ongoing complete response sequentially underwent one or more additional infusions of CAR T-cell targeting CD22 followed by CD20 according to their disease status and CAR T-cell persistence after each infusion. The median time from the last infusion to cutoff date was 17 months (range, 15 to 23). The estimated 18-month complete response rate was 78% (95% confidence interval [CI], 54 to 91). The estimated 18-month progression-free survival rate was 78% (95% CI, 55 to 90), with 78% (95% CI, 37 to 94) in patients with bulky diseases and 60% (95% CI, 25 to 83) in patients with central nervous system (CNS) involvement. During the first CD19 CAR T-cell infusion, grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity occurred in 34.8% and 21.7% of all patients, respectively. During subsequent infusions, few incidences of higher than grade 2 CRS and neurotoxicity were observed. All adverse events were reversible. The severity of neurotoxicity was not significantly different between patients with CNS and non-CNS involvement. Sequential CAR T-cell therapy may result in a durable response and is safe in pediatric refractory/relapsed Burkitt lymphoma. Patients with CNS involvement may benefit from sequential CAR T-cell therapy. This trial was registered at www.chictr.org.cn/index.aspx as ChiCTR1800014457.