Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells

• Published in: Clinical immunology (Orlando, Fla.) Vol. 155; no. 2; pp. 160 - 175
• Main Authors: Wang, Yao, Zhang, Wen-ying, Han, Qing-wang, Liu, Yang, Dai, Han-ren, Guo, Ye-lei, Bo, Jian, Fan, Hui, Zhang, Yan, Zhang, Ya-jing, Chen, Mei-xia, Feng, Kai-chao, Wang, Quan-shun, Fu, Xiao-bing, Han, Wei-dong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014
• Subjects: Aged; Aged, 80 and over; Allergy and Immunology; Anti-CD20 chimeric antigen receptor (CAR) T cells; Antigens, CD20 - genetics; Antigens, CD20 - immunology; Antigens, CD20 - metabolism; Cell Line; Combined Modality Therapy; Cytotoxicity, Immunologic; Delayed toxicities; Diffuse large B-cell lymphoma (DLBCL); Female; Gene Dosage; Gene Order; Humans; Immunotherapy, Adoptive - adverse effects; Lymphocyte Count; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Large B-Cell, Diffuse - therapy; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Protein Binding; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Refractory advanced; T-Cell Antigen Receptor Specificity - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tomography, X-Ray Computed; Treatment Outcome; Tumor Necrosis Factor Receptor Superfamily, Member 9 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 9 - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 9 - metabolism; Refractory advanced; Anti-CD20 chimeric antigen receptor (CAR) T cells; Delayed toxicities; Diffuse large B-cell lymphoma (DLBCL)
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2014.10.002

Abstract We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3ζ moiety in patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). Seven patients were enrolled. One of the two patients with no bulky tumor obtained a 14-month durable and ongoing complete remission by cell infusion only, and another attained a 6-month tumor regression. Four of five patients with bulky tumor burden were evaluable for clinical efficacy, three of which attained 3- to 6-month tumor regression. Delayed toxicities related to cell infusion are directly correlated to tumor burden and tumor-harboring sites, and mainly included cytokine release symptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract and aggressive intrapulmonary inflammation surrounding extranodal lesions. These results show firstly that anti-CD20 CART cells can cause prolonged tumor regression in combination with debulking conditioning regimens for advanced DLBCL. This study is registered at www.clinicaltrials.gov as NCT01735604.