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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies
Na Wang1,2, Xuelian Hu1,2, Wenyue Cao1,2
1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
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. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526.
Insights
Sequential infusion of chimeric antigen receptor T cells targeting CD19 and CD22 offers a promising strategy against B-cell malignancies, demonstrating efficacy and safety while potentially reducing antigen-escape relapse.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Antigen-escape relapse is a significant obstacle to long-term disease control following CD19-directed therapies for B-cell malignancies.
- Dual-targeting strategies, specifically engaging both CD19 and CD22, are being explored to overcome this challenge.
Purpose of the Study:
- To evaluate the efficacy and safety of sequential infusion of chimeric antigen receptor T cells targeting both CD19 and CD22 (CAR19/22) in patients with refractory/relapsed B-cell malignancies.
- To assess the potential of this dual-targeting approach to mitigate antigen-escape relapse.
Main Methods:
- A pilot study involving 89 patients with refractory/relapsed B-cell malignancies.
- Sequential infusion of two single-specific, third-generation chimeric antigen receptor-engineered T cells (CAR19/22).
- Evaluation of response rates, progression-free survival (PFS), overall survival (OS), and adverse events, including cytokine release syndrome and neurotoxicity.
Main Results:
- In 51 acute lymphoblastic leukemia patients, a 96.0% minimal residual disease-negative response rate was observed, with a median PFS of 13.6 months and median OS of 31.0 months.
- In 38 non-Hodgkin lymphoma patients, an overall response rate of 72.2% was achieved, with a median PFS of 9.9 months and median OS of 18.0 months.
- Antigen-loss relapse occurred in only one patient; high-grade cytokine release syndrome (22.4%) and neurotoxicity (1.12%) were mostly reversible.
Conclusions:
- Sequential CAR19/22 T cell infusion demonstrates significant safety and efficacy in treating B-cell malignancies.
- This dual-targeting immunotherapy approach shows potential in reducing the incidence of antigen-escape relapse.
- CAR19/22 T cells represent a promising therapeutic option for patients with refractory/relapsed B-cell malignancies.
