复发/难治性侵袭性 B 细胞淋巴瘤患者自体移植后 CD19/CD22 CAR-T 细胞鸡尾酒疗法

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 18 F-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.