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3492 Efficacy and Safety of Chimeric Antigen Receptor T Cells Therapy Strategy with Dual Targeting of CD19 and CD70 to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Lymphomas, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Sanfang Tu1*, Lijuan Zhou, MD1*, Rui Huang, MD2*, Xuan Zhou, MD1*, Jilong Yang, MD1*, Meifang Li, MD3*, Bo Jin, MD & PhD1*, Langqi Wang, MD1*, Yaqi Zhuo, MD1*, Huifang Chen, MD1*, Lung-Ji Chang, PhD4,5 and Yuhua Li1*

1Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
2Department of Hematology, Zhujiang Hospital, Southern Medical University, GUANGZHOU, AL, China
3Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou, China
4School of Medicine, University of Electronic Science and Technology of China, Chengdu, Chengdu, China
5Geno-Immue Medical Institute, Shenzhen, China

Background: Chimeric antigen receptor (CAR) T cells therapy is highly effective in the treatment of B-cell lymphoma, providing alternative therapeutic options for patients who failed to respond to conventional treatment or relapse. Despite impressive progress, more than 30-50% of patients treated with CD19 CAR-T cells experienced progressive disease. Antigen escape is one of the common causes of relapse, especially CD19-negative relapse. Absent or decreased cell surface CD19 as a mechanism of resistance after CD19 CAR-T cells treatment. CD70 is a novel and promising therapeutic target due to the restricted expression pattern in normal tissues and over expression in some lymphoma tissues. Our center explored the efficacy and safety of CAR-T cells therapy with dual targeting of CD19 and CD70 in the treatment of r/r lymphoma.

Patients and Methods: The study included 8 relapsed/refractory diffuse large B-cell lymphoma patients, all patients have exhausted all available treatment options with progressive or stable disease and life expectancy >2 months were enrolled in the study. All patients expressed strong positivity of CD19 and CD70, all of patient details can be found in the table (Fig.1). Autologous T cells were apheresis collected and transduced with an apoptosis-inducible, safety-engineered lentiviral CAR with the following intracellular signaling domains: CD28/CD27/CD3z-iCasp9. All patients received cyclophosphamide/fludarabine chemotherapy conditioning 1-2 days before infusions of CAR-T cells. The quality of apheresis cells, efficiencies of gene transfer and T cell proliferation, CAR-T infusion dose and blood CAR copies were quantitatively documented.

Results: In the first months after CAR-T cells infusion, 75.0% (6/8) of patients achieved complete response (CR), while 12.5% (1/8) of patients evaluated as partial response (PR) and 12.5% (1/8) of patients as progressive disease (PD), overall response rate (ORR) is 87.5% (7/8). In the evaluation of safety, 37.5% (3/8) of patients experienced cytokine release syndrome (CRS), and 25% (2/8) of patients experienced grade 1 CRS and 12.5% (1/8) of patients experienced grade 2 CRS, no case of severe CRS defined as≥grade 3 and no immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. After a median follow-up of 19.9 months, 50% (4/8) of patients maintained CR, while 37.5% (3/8) of patients were relapsed, with a duration of response (DOR) of 50% (4/8), median DFS was 10.5 months and median OS was not reached (Fig.2).

Conclusions: In summary, our research data confirms that the efficacy and safety of CD19/CD70 dual targeted CAR-T cells infusion, continued follow-up will determine whether the CD19/CD70 CAR-T cells therapy can obtain long term overall survival in our study. How to further improve the efficacy and safety of dual target CAR-T is still worth exploring. It’s needed to optimize multi-specific targeting by CAR-T cells to improve the efficacy both in B cell malignancies and other hematological malignancies.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH