Sequential infusion of CAR19/22 T-cell is highly active and well-tolerated in patients with refractory/relapsed B-cell malignancies.
Dual-targeting of CD19 and CD22 may represent a feasible solution to reduce antigen escape relapse after CD19/CD22-directed therapies.
Antigen escape relapse has emerged as a major challenge for long-term disease control post CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. Between March 2016 and January 2018, we conducted a pilot study in 89 patients, who had refractory/relapsed B-cell malignancies, to evaluate the efficacy and safety of sequential infusion of anti-CD19 and anti-CD22, two single-specific, third-generation chimeric antigen receptor-engineered (CAR19/22) T-cell "cocktail". Among the 51 patients with acute lymphoblastic leukemia, the minimal residual disease-negative response rate was 96.0% (95% confidence interval (CI), 86.3 to 99.5). With a median follow-up of 16.7 months (range, 1.3 to 33.3), the median progression-free survival (PFS) was 13.6 months (95% CI, 6.5 to not reached, NR), and the median overall survival (OS) was 31.0 months (95% CI, 10.6 to NR). Among the 38 patients with non-Hodgkin lymphoma, the overall response rate was 72.2% (95% CI, 54.8 to 85.8), with a complete response rate of 50.0% (95% CI, 32.9 to 67.1). With a median follow-up of 14.4 months (range, 0.4 to 27.4), the median PFS was 9.9 months (95% CI, 3.3 to NR), and the median OS was 18.0 months (95% CI, 6.1 to NR). Antigen loss relapse occurred in one patient during follow-up. High-grade cytokine release syndrome and neurotoxicity occurred in 22.4% and 1.12% patients, respectively. All except one were reversible. Our results indicated that sequential infusion of CAR19/22 T-cell was safe, efficacious, and may have reduced the rate of antigen escape relapse in B-cell malignancies. ChiCTR, number ChiCTR-OPN-16008526.