Relapse remains a major limitation of CD19-directed chimeric antigen receptor (CAR) T-cell therapy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Although CD19 CAR T-cell treatment can induce high initial remission rates, disease recurrence—often driven by antigen loss or lineage escape—continues to compromise long-term outcomes. In response to this challenge, investigators at GoBroad Healthcare Group explored a sequential CAR T-cell strategy targeting both CD19 and CD22 to enhance remission durability and reduce relapse risk in pediatric patients.

This phase 2 clinical study was conducted at Beijing GoBroad Boren Hospital and enrolled children and adolescents aged 1 to 18 years with relapsed or refractory B-ALL expressing high levels of both CD19 and CD22. Patients first received an intravenous infusion of CD19-directed CAR T cells. Once deep remission was achieved, defined as minimal residual disease–negative complete remission or complete remission with incomplete hematologic recovery, and after non-hematologic toxicities had resolved to an acceptable level, patients proceeded to CD22-directed CAR T-cell infusion. Both infusions were administered within a predefined target dose range designed to balance efficacy and safety.

Between May 2020 and August 2022, 81 pediatric patients were enrolled in the study. Nearly all patients completed the planned sequential treatment, with a median interval of just over one month between the two infusions. Among patients who received the target dose, the vast majority achieved an objective response within three months of initiating therapy, demonstrating the strong antileukemic activity of the sequential approach. With extended follow-up, survival outcomes remained favorable, with high rates of event-free survival, disease-free survival, and overall survival observed at 18 months.

The safety profile of sequential CD19- and CD22-directed CAR T-cell therapy was consistent with expectations for cellular immunotherapy in this population. The most common severe adverse events were hematologic toxicities, reflecting both prior treatment burden and on-target effects of CAR T-cell therapy. Cytokine release syndrome and neurotoxicity were generally manageable, and serious late non-hematologic toxicities were uncommon. Importantly, no treatment-related deaths were reported. Pharmacokinetic analyses confirmed robust in vivo expansion of CAR T cells following both infusions, and sustained B-cell aplasia in most evaluable patients indicated prolonged biological activity.

Collectively, these findings demonstrate that sequential targeting of CD19 and CD22 can induce deep and durable remissions with an acceptable safety profile in children with relapsed or refractory B-ALL. This strategy offers a promising approach to overcoming antigen escape and improving long-term disease control in a high-risk pediatric population. The study highlights GoBroad Healthcare Group’s continued leadership in advancing innovative CAR T-cell therapies and translating clinical research into meaningful outcomes for patients and families.

Refer to the original:https://doi.org/10.1016/S1470-2045(23)00436-9