CLIC-1901

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Chimeric antigen receptor (CAR) modified T cells targeting CD19 hold great promise to improve the complete response rates of DLBCL patients compared with conventional therapies. Here, we conducted a clinical trial to evaluate the efficacy and safety of CAR-T cells. Five patients with relapsed or refractory DLBCL were treated with autologous T cells expressing the 19-41BBz chimeric antigen receptor (CAR) specifically targeted the CD19 antigen (IM19 CAR-T). The development of cytokine release syndrome (CRS) was observed. And the efficacy of IM19 CAR-T cell treatment was measured with positron emission tomography (PET)-computed tomography (CT). Of the four patients evaluable for response, two obtained complete responses (CRs), one obtained partial response (PR), and one had stable disease (SD). Remarkably, among the five patients, only one developed grade 2 CRS while the others only elicited grade 1 CRS. Additionally, the efficacy and safety of IM19 CAR-T cells were correlated with the peak blood level and persistence of CAR-T cells, as well as the immunophenotype of T-cell subsets. Overall, this study indicates the feasibility and effectiveness of IM19 CAR-T cells in the treatment of refractory or relapsed diffuse large B-cell lymphoma.

Purpose: Chimeric Antigen Receptor T(CAR-T) cell therapy is an immunotherapy approach used in treating cancer which has seen rapid development over the decades. It becomes the preferred treatment choice after patients have failed conventional chemotherapy. Methods: We conducted a meta-analysis in 320 patients from 14 studies to estimate the survival outcome, response rate and toxicity of autologous CD19 CAR-T cell therapy and predict other factors associated with a better prognosis. Results: The overall response rate was 71.88% (95% CI: 61.34-80.46%, p<0.01) and CRS toxicity was 60.15% (95% CI: 42.87-75.22%, p<0.01). Patients who received lymphodepletion was associated with a better response rate (77%, 95%CI: 67-83%; p-value =0.001) in comparison to the other patients who did not (66%, 95%CI: 41-83%). Conclusion: Lymphodepletion regimen may play a crucial role in predicting the prognosis of patients with hematological malignancies. Lymphodepletion patients had better progression-free survival than those who did not.