In a Chinese single-center phase II study reported in The Lancet Oncology, Pan et al found that sequential CD19- and CD22-directed chimeric antigen receptor (CAR) T-cell therapy was active in pediatric patients with refractory or relapsed B-cell acute lymphocytic leukemia (ALL).
Study Details
In the study, 81 patients aged 1 to 18 years (median = 8 years, interquartile range [IQR] = 6–10 years) with CD19 and CD22 positivity > 95% were enrolled at Beijing GoBroad Boren Hospital between May 2020 and August 2022. Patients initially received an infusion of CD19-directed CAR T cells; infusion of CD22-directed CAR T cells was performed when measurable residual disease (MRD)-negative complete remission (or complete remission with incomplete hematologic recovery) was achieved and all adverse events except hematologic adverse events were grade 2 or better. The target dose for each infusion was 0.5 × 10⁶ to 5.0 × 10⁶ cells/kg. The primary endpoint was rate of objective response (MRD-negative complete remission or complete remission with incomplete hematologic recovery) at 3 months after the first infusion in patients receiving the target dose.
Key Findings
All 81 patients received the first infusion, and 79 patients (98%) received sequential infusions, with CD19-directed CAR T cells given at a median dose of 2.7 × 10⁶ cells/kg and CD22-directed CAR T cells at a median dose of 2.2 × 10⁶ cells/kg; median interval between infusions was 39 days (IQR = 37–41 days). A total of 62 patients (77%) received the target dose.
At 3 months, objective response was observed in 60 of 62 patients (97%, 95% confidence interval [CI] = 89%–100%) who received the target dose and in 79 of all 81 patients (98%, 95% CI = 91%–100%).
Median follow-up was 17.7 months (IQR = 11.4–20.9 months). Event-free survival among patients receiving the target dose was 85% (95% CI = 75%–95%) at 12 months and 79% (95% CI = 66%–91%) at 18 months. Event-free survival among all 81 patients was 83% (95% CI = 74%–92%) at 12 months and 78% (95% CI = 67%–89%) at 18 months. Overall survival among both patients receiving the target dose and all patients was 96% (95% CI = 91%–100%) at both 12 and 18 months.
At data cutoff, 35 of 77 evaluable patients (45%) had CAR transgenes, and 59 (77%) had B-cell aplasia. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR = 7–14 days) after CD19-directed and 12 days (IQR = 10–15 days) after CD22-directed CAR T-cell infusion.
Common grade 3 or 4 adverse events included cytopenias (79%), cytokine-release syndrome (19%), neurotoxicity (5%), and infections (6%). Nonhematologic grade ≥ 3 adverse events occurred in 8% of patients. No treatment-related deaths were reported.
The investigators concluded: “This sequential strategy induced deep and sustained responses with an acceptable toxicity profile and thus potentially provides long-term benefits for children with this condition.”
Jing Pan, MD, of Boren Clinical Translational Center, Department of Hematology, Beijing GoBroad Boren Hospital, Beijing, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the National Key Research & Development Program of China, CAMS Innovation Fund for Medical Sciences, and Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences. For full disclosures of the study authors, visit thelancet.com.
