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.
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The dataset(s) supporting the findings of this study are included within the article.
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This work was supported by Beijing Natural Science Foundation (7132183), China Health Promotion Foundation (CHPF-zlkysx-001), Key project of Peking University Third Hospital (BYSY2015004), Zhongguancun Frontier Reserve Project, Beijing Science and Technology SME Promotion Project, Beijing Science and Technology Rising Star Project and Beijing Eagle Talent Project. CAR-T cells in this study were provided by Beijing Immunochina Medical Science & Technology Co., Ltd. The clinical trial in this study was also sponsored by Beijing Immunochina Medical Science & Technology Co., Ltd.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval and consent to participate
This study was performed in accordance with the Declaration of Helsinki and approved by the Peking University Third Hospital Institutional Review Board. All patients enrolled in this trial gave written informed consent after a discussion of the possible risks and adverse effects of the therapy.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Trial registration: NCT03344705, Registered November 14, 2017, Prospective clinical trial. https://www.clinicaltrials.gov/ct2/show/NCT03344705?term=immunochina&rank=1
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Bao, F., Wan, W., He, T. et al. Autologous CD19-directed chimeric antigen receptor-T cell is an effective and safe treatment to refractory or relapsed diffuse large B-cell lymphoma. Cancer Gene Ther 26, 248–255 (2019). https://doi.org/10.1038/s41417-018-0073-7
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