In a Chinese phase II study reported in the Journal of Clinical Oncology, Wang et al found that the coadministration of CD19- and CD22-directed chimeric antigen receptor (CAR) T cells produced promising initial outcomes in pediatric patients with B-cell acute lymphoblastic leukemia (ALL) with refractory disease, hematologic relapse, or isolated extramedullary relapse.
Study Details
In the multicenter trial, 225 evaluable patients, enrolled between September 2019 and December 2021, received a single infusion of combined CD19- and CD22-directed CAR T cells at a median dose of 5.6 × 106/kg for those with refractory disease or hematologic relapse (n = 194) and 7.0 × 106/kg in those with extramedullary relapse (n = 31).
Responses
Complete remission was achieved in 192 (99.0%) of 194 patients with refractory disease or hematologic relapse, with all remissions being negative for measurable residual disease. Among these patients, the 12-month event-free survival rate was 73.5% (95% confidence interval [CI] = 67.3%–80.3%). Relapse occurred in 43 patients (CD19+/CD22+ relapse in 24, CD19-/CD22+ in 16, CD19-/CD22- in 1, and unknown in 2).
Among 78 patients receiving consolidative transplantation, the 12-month event-free survival rate was 85.0% (95% CI = 77.2%–93.6%), compared with 69.2% (95% CI = 60.8%–78.8%) among 116 not undergoing transplantation (P = .03). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months.
KEY POINTS
- Among patients with refractory disease or hematologic relapse, complete remission occurred in 99% and the 12-month event-free survival rate was 73.5%.
- Event-free survival at 12 months was 95.0% among patients with isolated testicular relapse and 68.6% among those with isolated central nervous system relapse.
Complete remission was achieved in all patients with extramedullary relapse. The event-free survival rate at 12 months was 95.0% (95% CI = 85.9%–100%) among 20 patients with isolated testicular relapse and 68.6% (95% CI = 44.5%–100%) among 10 with isolated central nervous system relapse. One patient with combined testicular and central nervous system relapse remained in complete remission for 14.4 months.
Adverse Events
Cytokine-release syndrome occurred in 198 patients (88.0%), was grade ≥ 3 in 64 (28.4%), and resulted in death in 1 patient. Neurotoxicity occurred in 47 patients (20.9%), was grade ≥ 3 in 9 (4.0%), and resulted in death in 2 patients. Grade 3 or 4 seizures occurred in 14.2% of patients; grade 3 or 4 hypotension occurred in 40.9%. Tocilizumab was given to 167 patients (74.2%) and corticosteroids to 79 (35.1%).
The investigators concluded, “CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-[cell] ALL, including those with isolated or combined extramedullary relapse.”
Ching-Hon Pui, MD, of the Departments of Oncology, Pathology and Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Natural Science Foundation of China, Shanghai Collaborative Innovation Center for Translational Medicine, Research Programs of Shanghai Science and Technology Commission Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
