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

Yao Wang, Wen-ying Zhang, Qing-wang Han, Yang Liu, Han-ren Dai, Ye-lei Guo, Jian Bo, Hui Fan, Yan Zhang, Ya-jing Zhang, Mei-xia Chen, Kai-chao Feng, Quan-shun Wang, Xiao-bing Fu, Wei-dong Han
Clinical Immunology: the Official Journal of the Clinical Immunology Society 2014, 155 (2): 160-75
25444722
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.

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