American Association for Cancer Research
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Figure S1 from Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma

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posted on 2023-03-31, 21:12 authored by Zi-Xun Yan, Li Li, Wen Wang, Bin-Shen OuYang, Shu Cheng, Li Wang, Wen Wu, Peng-Peng Xu, Muharrem Muftuoglu, Ming Hao, Su Yang, Mu-Chen Zhang, Zhong Zheng, James Li, Wei-Li Zhao

Supplementary Figure S1. PET-CT and CT evaluation of the partial remission patients before CAR T treatment and on Day 29 after treatment.


National Natural Science Foundation of China

Chang Jiang Scholars Program, Shanghai Commission of Science and Technology

Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant



Anti-CD19 chimeric antigen receptor (CAR) T cells represent a novel immunotherapy and are highly effective in treating relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL). How tumor microenvironment influences clinical response to CAR T therapy remains of great interest. A phase I, first-in-human, dose-escalation study of anti-CD19 JWCAR029 was conducted in refractory B-NHL (NCT03355859) and 10 patients received CAR T cells at an escalating dose of 2.5 × 107(n = 3), 5 × 107(n = 4), and 1 × 108(n = 3) cells. Core needle biopsy was performed on tumor samples collected from diffuse large B-cell lymphoma patients on Day −6 (1 day before lymphodepletion) and on Day 11 after CAR T-cell infusion when adequate CAR T-cell expansion was detected. The overall response rate was 100%, with 6 of 9 (66.7%) evaluable patients achieving complete remission. The most common adverse events of grade 3 or higher were neutropenia (10/10, 100%), anemia (3/10, 30%), thrombocytopenia (3/10, 30%), and hypofibrinogenemia (2/10, 20%). Grade 1 cytokine release syndrome occurred in all patients and grade 3 neurotoxicity in 1 patient. The average peak levels of peripheral blood CAR T cells and cytokines were similar in 3 different dose levels, but CAR T cells were significantly higher in patients achieved complete remission on Day 29. Meanwhile, RNA sequencing identified gene expression signatures differentially enriched in complete and partial remission patients. Increased tumor-associated macrophage infiltration was negatively associated with remission status. JWCAR029 was effective and safe in treating refractory B-NHL. The composition of the tumor microenvironment has a potential impact in CAR T therapy response.

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