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
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.
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