Journal
BLOOD
Volume 135, Issue 1, Pages 17-27Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019000017
Keywords
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Funding
- Key Program of the National Natural Science Foundation of China [81830008, 81630006]
- National Natural Science Foundation of China [81670152, 81600120, 81570197, 81873452, 81873444]
- Natural Science Foundation of Hubei Province [2018ACA140, 2016CFA011]
- Huanghe Talents Plan of Wuhan City [HHYC-2015002]
- National High Technology Research and Development Program of China (863 Program) [2014AA020532]
- Applied Basic Research Project of Wuhan City [2017060201010156]
- Milstein Medical Asian American Partnership (MMAAP) Foundation (2018 MMAAP Foundation Hematology Fellowship Award)
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Antigen-escape relapse has emerged as a major challenge for long-term disease control after CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. From March 2016 through 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, a cocktail of 2 single-specific, third-generation chimeric antigen receptor-engineered (CAR19/22) T cells. Among the 51 patients with acute lymphoblastic leukemia, the minimal residual disease-negative response rate was 96.0% (95% confidence interval [CI], 86.3-99.5). With a median follow-up of 16.7 months (range, 1.3-33.3), 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-NR). Among the 38 patients with non-Hodgkin lymphoma, the overall response rate was 72.2% (95% CI, 54.8-85.8), with a complete response rate of 50.0% (95% CI, 32.9-67.1). With a median follow-up of 14.4 months (range, 0.4-27.4), the median PFS was 9.9 months (95% CI, 3.3-NR), and the median OS was 18.0 months (95% CI, 6.1-NR). Antigen-loss relapse occurred in 1 patient during follow-up. High-grade cytokine release syndrome and neurotoxicity occurred in 22.4% and 1.12% patients, respectively. In all except 1, these effects were reversible. Our results indicated that sequential infusion of CAR19/22 T cell was safe and efficacious and may have reduced the rate of antigen-escape relapse in B-cell malignancies.
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