A follow-up study investigating the coadministration of CD19- and CD22-targeted chimeric antigen receptor (CAR) T-cell therapy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) found the therapy is safe and effective and achieved durable remissions in these patients, including those with isolated or combined extramedullary relapse. The study by Wan et al was presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 681).

Study Methodology

In this investigator-initiated clinical trial using a new bicistronic construct, the researchers enrolled 318 evaluable patients, aged ≤ 18 years, between January 2022 and April 2024. The median follow-up for patients who were alive at the time of the analysis was 13.9 months (interquartile range = 9.0–22.4 months). The researchers evaluated clinical responses, treatment side effects, and the expansion and persistence of CAR T cells.

Results

The study showed a 99.1% response rate to the therapy among the 318 patients, all of whom were measurable residual disease–negative (< 0.01%). The 12-month event-free survival and overall survival rates for 267 patients with isolated or combined hematologic relapse were 72.4% and 91.4%, respectively.

Consolidative transplantation was associated with favorable outcomes and was performed in 37 (13.9%) of 267 patients. The 12-month event-free survival was 86.0% for those who underwent transplantation vs 71.4% for those who did not (P = .04). However, transplantation did not provide a significant benefit with regard to overall survival—12-month overall survival rates were 94.2% for patients who had transplants and 92.2% for those who did not (P = .86).

Among the 230 patients who did not undergo transplantation after CAR T-cell therapy, 69 patients relapsed (45 with CD19-positive/CD22-positive expression; 23 with CD19-negative/CD22-positive expression; and 1 with CD19-negative/CD22-negative expression). Most patients were treated with a second salvaged bicistronic CD19/CD22–targeted CAR T-cell therapy, achieving complete remission again in 35 (97.2%) of 36 CD19-positive/CD22-positive patients and 14 (66.7%) of 21 CD19-negative/CD22-positive patients.

Among the 49 patients who achieved complete remission, 42 (85.7%) were still in remission for 1.0 to 22.1 months, 30 of whom received consolidative transplantation. For the 20 patients with isolated testicular relapse, the 12-month event-free survival and overall survival rates were 84.7% and 100.0%, respectively. For the 29 patients with isolated central nervous system relapse, the 12-month event-free survival and overall survival rates were 71.0% and 96.2%, respectively.

All patients developed cytokine-release syndrome, which was grade 3 or 4 in 155 patients (48.7%) and resulted in two deaths. CAR T-cell neurotoxicity was observed in 52 patients (16.4%).

“Bicistronic CD19/CD22–targeted CAR T-cell therapy is a safe and effective regimen which achieved durable remission in children with relapsed or refractory [B-cell] ALL, including those with isolated or combined extramedullary relapse,” concluded the study authors.

Disclosure: The study authors reported no conflicts of interest.