CD19/CD22 Chimeric Antigen Receptor T Cell Cocktail Therapy following Autologous Transplantation in Patients with Relapsed/Refractory Aggressive B Cell Lymphomas
Yang Cao, Yi Xiao, Na Wang, Gaoxiang Wang, Liang Huang, Zhenya Hong, Meng Li, Xiaoxi Zhou, Jue Wang, Yang Yang, Hao Xu, Shangkun Zhang, Min Xiao, Liting Chen, Miao Zheng, Chunrui Li, Xia Mao, Chaojiang Gu, Tongcun Zhang, Yicheng Zhang, Jianfeng Zhou
Abstract
High-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) is the standard of care for chemosensitive relapsed or refractory (R/R) aggressive B cell lymphoma. Patients with a positive positron emission tomography (PET) scan before ASCT have a poor prognosis, and those who fail to achieve a therapeutic response better than partial remission after salvage treatment are ineligible candidates for ASCT. We conducted this open-label single-arm prospective clinical study to evaluate the safety and efficacy of sequential infusion of CD19/22 chimeric antigen receptor (CAR) T cells following HDT-ASCT. Eligibility for this study included patients with R/R aggressive B cell non-Hodgkin lymphoma (B-NHL) with 18F-fluorodeoxyglucose-PET positivity and patients with stable or progressive disease after salvage chemotherapy. Between November 14, 2016, and August 15, 2019, 42 patients underwent HDT-ASCT followed by CD19/22 CAR T cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in only 2 patients. Twenty-one percent of patients experienced any grade of neurotoxicity, 5% with severe grade 3. All cases of CRS and neurotoxicity were reversible. The overall response rate was 90.5% (95% confidence interval [CI], 77.4% to 97.3%). At a median follow-up of 24.3 months, the median progression-free survival (PFS) and overall survival were not reached. The 2-year PFS rate was 83.3 % (95% CI, 68.2% to 91.7%). No patients were found to be CD19- and CD22-negative at the time of progression; 97.1% and 68.6% of patients with ongoing complete remission (CR) had consistently detectable levels of CD19 and CD22 CAR transgene, respectively, at 3 months. The median time to onset of sustained B cell recovery was 8.2 months. The high durable CR rates and favorable safety profiles support the strong potential of the HDT-ASCT plus CD19/CD22 CAR T cell cocktail therapy for the suboptimal group of patients with R/R aggressive B-NHL who are less sensitive or fail salvage chemotherapy. These early data are encouraging and informative for future trials to further test the efficacy and safety of HDT-ASCT plus CAR T cell therapy in a larger population. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.