决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Efficacy of Multiple SARS-CoV-2 Vaccine Doses in Patients with B Cell Hematologic Malignancies Receiving Chimeric Antigen Receptor T Cell Therapy: A Contemporary Cohort Analysis.
Efficacy of Multiple SARS-CoV-2 Vaccine Doses in Patients with B Cell Hematologic Malignancies Receiving Chimeric Antigen Receptor T Cell Therapy: A Contemporary Cohort Analysis.
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严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)在嵌合抗原受体(CAR)T 细胞治疗(CAR-T)接受者中的死亡率接近 40%。
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在嵌合抗原受体(CAR)T细胞治疗(CAR-T)接受者中的死亡率接近40%。重复接种疫苗剂量(包括二价加强针)的疗效仍不清楚。我们研究了在T细胞输注后接受至少2剂或更多疫苗剂量的CAR-T 接受者中重复接种疫苗剂量的疗效。这项单中心回顾性研究纳入了2018年9月至2022年3月期间因靶向CD19、BCMA或CD19和CD20的复发/难治性(R/R)B细胞血液系统恶性肿瘤而接受CAR-T 治疗、且存活至2021年以后以接受递增SARS-CoV-2疫苗剂量并有可用血清转化数据的年龄>18岁成人。多变量分析采用设计校正的Cox回归和logistic回归方法并进行分层。在多变量分析中,总共接种4剂或更多疫苗剂量时,血清转化率显著更高(比值比[OR],8.22;P = .008)。与其他B细胞血液系统恶性肿瘤的CAR-T 接受者相比,R/R多发性骨髓瘤患者的血清转化率显著更低,Ab滴度也降低(OR,.07;P = .003)。在这个接种疫苗的研究队列中,有1例患者死于COVID-19,占COVID-19归因死亡率的1.7%。这些结果提供了一个当代队列中的基线疫苗应答数据,该队列包括感染不同SARS-COV2变异株的患者,并支持美国疾病控制与预防中心关于针对当前流行关注变异株重复接种疫苗的最新指南。
The mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) approaches 40% in recipients of chimeric antigen receptor (CAR) T cell therapy (CAR-T). The efficacy of repeated vaccine doses, including bivalent boosters, remains unknown. We examined the efficacy of repeated vaccine doses among CAR-T recipients who received at least 2 or more vaccine doses after T cell infusion. This single-center retrospective study included adults age >18 years receiving CAR-T for relapsed/refractory (R/R) B cell hematologic malignancies targeting CD19, BCMA, or CD19 and CD20 between September 2018 through March 2022 and were alive beyond 2021 to receive incremental SARS-CoV-2 vaccine doses with available seroconversion data. Multivariable analyses were performed using the design-adjusted Cox regression and logistic regression approaches with stratification. In multivariable analysis, seroconversion rates were significantly greater with a total of 4 or more vaccine doses (odds ratio [OR], 8.22; P = .008). CAR-T recipients with other B cell hematologic malignancies had significantly lower seroconversion rates and diminished Ab titers compared to those with R/R multiple myeloma (OR, .07; P = .003). One patient died due to COVID-19 in this vaccinated study cohort, accounting for a COVID-19-attributable mortality rate of 1.7%. The results provide baseline vaccine response data in a contemporary cohort including patients with diverse group of SARS-COV2 variants and support the latest Centers for Disease Control and Prevention guidelines for repeated vaccinations directed against the prevalent variant of concern.
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