Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis.Chimeric Antigen Receptor(CAR)-modified T cells(CART cells)that targeted CD20 were effective in a phase I clinical trial for patients w...Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis.Chimeric Antigen Receptor(CAR)-modified T cells(CART cells)that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas.We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART(CART-20)cells to patients with refractory or relapsed CD20^(+)B-cell lymphoma.Eleven patients were enrolled,and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions.The overall objective response rate was 9 of 11(81.8%),with 6 complete remissions(CRs)and 3 partial remissions;no severe toxicity was observed.The median progression-free survival lasted for 46 months,and 1 patient had a 27-month continuous CR.A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed.Clinically,the lesions in special sites,specifically the spleen and testicle,were refractory to CART-20 treatment.Collectively,these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study.This study was registered at www.clinicaltrials.org as NCT01735604.展开更多
基金This study was supported by the grants from the National Natural Science Foundation of China(Nos.31270820,81230061,81121004 and 81402566)was partially supported by a grant from the National Basic Science and Development Programme of China(Nos.2012CB518103,2012AA020502 and 2013BAI01B00).
文摘Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis.Chimeric Antigen Receptor(CAR)-modified T cells(CART cells)that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas.We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART(CART-20)cells to patients with refractory or relapsed CD20^(+)B-cell lymphoma.Eleven patients were enrolled,and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions.The overall objective response rate was 9 of 11(81.8%),with 6 complete remissions(CRs)and 3 partial remissions;no severe toxicity was observed.The median progression-free survival lasted for 46 months,and 1 patient had a 27-month continuous CR.A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed.Clinically,the lesions in special sites,specifically the spleen and testicle,were refractory to CART-20 treatment.Collectively,these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study.This study was registered at www.clinicaltrials.org as NCT01735604.
