Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Lymphomas, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Combination therapy, Diseases, Therapies, Lymphoid Malignancies
Patients and Methods: The study included 6 r/r DLBCL patients, 4 patients have previously received 3-line or above treatment, and 2 patients began CAR-T treatment after 1-line chemotherapy. All patients received fludarabine (FLU) and cyclophosphamide (CTX) conditioning chemotherapy (FLU 30mg/m2. d1-3; CTX 500mg/m2, d1-3) before CAR-T infusions. T cells were apheresis collected and transduced with a lentiviral CD19 scFv CAR fused with intracellular signaling domains: CD28/CD27/CD3z-iCasp9. CAR-T cells were infused at dose of 2.0x106 cells/kg. The quality of apheresis cells, gene transfer and T cell proliferation efficiencies, and effective CAR-T infusion dose were quantitatively scored and documented. All patients began to combine with zanubrutinib after one month of CAR-T cells infusion.
Results: After one month of CAR-T cells infusion, total of 50% (3/6) of patients achieved complete response (CR), while 50%(3/6) of patients were evaluated as partial response (PR), with an overall response rate (ORR) of 100%. Within 6 months after combined with zanubrutinib, all patients of PR achieved CR. In the evaluation of safety, 83% (5/6) of patients occurred grade 2 cytokine release syndrome (CRS), and 33.3% (2/6) patient occurred grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), no case of severe CRS defined as≥grade 3 occurred, 66.7% (4/6) of patients occurred grade 2 hematotoxicity and 33.3% (2/6) of patients occurred grade 4 hematotoxicity. After a median follow-up of 19.5 months, 6 patients maintained CR, with an duration of response (DOR) of 100%, median DFS and OS were not reached. All patients can be detected CAR-T cells sustain in peripheral blood mononuclear cells continuously until last follow-up date(Fig.2). Continued follow-up will confirm whether the CAR-T cells therapy combined with zanubrutinib can obtain long term overall survival in these study.
Conclusions: Our study proved that CD19 CAR-T Cells combined with zanubrutinib for the strategy of relapsed/refractory DLBCL and as maintenance treatment showed strong efficacy with acceptable toxicity, the current results already support that zanubrutinib in the treatment of r/r DLBCL is expected to reduce the risk of relapsed, thereby prolonging the disease-free survival of patients, without increasing the incidence of adverse effects. More follow-up and clinical trials are needed to clarify the efficacy of Chimeric Antigen Receptor T Cells Therapy combined with zanubrutinib in the treatment of r/r DLBCL.
Disclosures: No relevant conflicts of interest to declare.