101. Phase II trial of co‐administration of CD19‐ and CD20‐targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma
- Author
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Yuanyuan Ma, Xuguang Song, Feng Zhu, Hai Cheng, Haiying Sun, Depeng Li, Jiang Cao, Meixue Yao, Jingjing Yang, Kailin Xu, Ming Shi, Weidong Li, Cai Sun, Hui Liu, Jun Jiao, Mei Wu, Yuanyuan Qin, Linyan Xu, Kemeng Sun, Xiang Gao, Ying Wang, Junnian Zheng, Zhenyu Li, Bing Zhang, Lingyu Zeng, Zhiling Yan, Dongmei Yan, Tingting Sang, and Wei Sang
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Time Factors ,Transplantation Conditioning ,T-Lymphocytes ,Immunotherapy, Adoptive ,Gastroenterology ,CAR‐T ,0302 clinical medicine ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,Refractory Diffuse Large B-Cell Lymphoma ,Original Research ,CD20 ,B-Lymphocytes ,Receptors, Chimeric Antigen ,biology ,CD19 ,Anemia ,clinical trial ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Progression-Free Survival ,Fludarabine ,Cytokine release syndrome ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Female ,Lymphoma, Large B-Cell, Diffuse ,Cytokine Release Syndrome ,Glycolysis ,Vidarabine ,medicine.drug ,Adult ,medicine.medical_specialty ,Neutropenia ,Cyclophosphamide ,Antigens, CD19 ,CD4-CD8 Ratio ,Antineoplastic Agents ,lcsh:RC254-282 ,Young Adult ,03 medical and health sciences ,Antigen ,Internal medicine ,Confidence Intervals ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Ifosfamide ,Aged ,business.industry ,Clinical Cancer Research ,Antigens, CD20 ,medicine.disease ,Thrombocytopenia ,030104 developmental biology ,DLBCL ,biology.protein ,business ,Diffuse large B-cell lymphoma - Abstract
Purpose Anti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 and anti‐CD20 CAR‐T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity. Methods Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti‐CD19 and anti‐CD20 CAR‐T cells. Treatment response, toxicity, and persistence were monitored continuously. Results Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%‐94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%‐74.3%) had a complete response (CR). Peak levels of anti‐CD19 and anti‐CD20 CAR cells were associated with response (P = .007 and .002). Grade 3‐4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression‐free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level. Conclusions Coadministration of anti‐CD19 and CD20 CAR‐T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178., In this study, we confirmed that combination of anti‐CD19 and anti‐CD20 CAR‐T cells therapy strategy was efficient (81% ORR and 52.4% CR respectively) for R/R DLBCL, and that the toxicities was transient and manageable. To our knowledge, this is the first report that combination of anti‐CD19 and anti‐CD20 double‐target CAR‐T cell therapy for R/R DLBCL, and our data demonstrated the feasibility of combination of anti‐CD19 and anti‐CD20 CAR‐T cells therapy for R/R DLBCL.
- Published
- 2020