J Clin Oncol: CD19 and CD22 targeting chimeric antigen receptor T cells in combination therapy for childhood B-cell acute lymphoblastic leukemia

Spiegel et al.
of Stanford University in the United States have developed bispecific CAR-T cells targeting CD19 and CD22 to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and large B-cell lymphoma (LBCL).

The study is a Phase II clinical trial to evaluate the safety and efficacy
of CD19 and CD22 chimeric antigen receptor T cells in combination in patients with refractory disease or high-risk hematological disorders or extramedullary recurrence of B acute lymphoblastic leukemia.

Between 17 September 2019 and 31 December 2021, a total of 225 patients
aged ≤ 20 years were enrolled.
The researchers first conducted a safe run-in phase to determine the recommended dose
.

Event-free survival in patients receiving CD19/CD22 CAR T cell or CD19 CAR T cell therapy

Of the 194 patients with refractory leukemia or recurrent blood disease, 99.
0% achieved complete remission, and all minimal residual lesions were negative
.
Its 12-month event-free survival rate (EFS) was 73.
5
%.
Recurrence occurred in 43 patients (24 CD19+/CD22+ recurrences, 16 CD19-/CD22+ recurrences, 1 CD19-/CD22- recurrence, and two unspecified recurrences).

Consolidation transplantation and persistent B-cell aplasia at 6 months are associated with
a good prognosis.
The 12-month EFS of 78 patients treated with transplantation was 85.
0%; The 12-month EFS of the 116 patients who did not receive transplant treatment was 69.
2% (p=0.
03).

All 25 patients with 6 months of persistent B-cell aplasia remained in remission at 12 months
.
The 12-month EFS of 20 patients with isolated testicular recurrence was 95.
0%; The 12-month EFS of 10 patients with isolated CNS recurrence was 68.
6%.

Event-free survival in patients with isolated testicular or CNS recurrence

Cytokine release syndrome occurred in 198 (88.
0%) patients, and CAR T cell neurotoxicity occurred in 47 (20.
9%) patients, resulting in 3 deaths
.

In summary, CD19-/CD22-CAR-T cell therapy has achieved relatively durable remission in children with relapsed or refractory B acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse
.

Original source:

Tianyi Wang, et al.
Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.
J Clin Oncol.
November, 2022.
https://ascopubs.
org/doi/abs/10.
1200/JCO.
22.
01214?role=tab