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:Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab.
这些结果证明了BsAbs在R/R DLBCL中的活性,并强调了靶抗原表达的重要性。
Epcoritamab和glofitamab是靶向CD20的双特异性抗体(BsAbs),已在美国获批用于复发或难治性(R/R)弥漫性大B细胞淋巴瘤(DLBCL)。在临床试验之外接受治疗的患者数据有限。收集了2023年1月1日至2024年10月15日期间在21家美国机构接受商业化epcoritamab或glofitamab治疗的R/R DLBCL患者。在245例患者中,156例接受epcoritamab,89例接受glofitamab,113例对一线治疗难治,40例具有MYC和BCL2和/或BCL6重排,147例既往接受过CAR-T 细胞治疗,174例不符合注册临床试验入组条件。Epcoritamab和glofitamab的总体缓解率(ORR)分别为51%(23%完全缓解,[CR])和53%(30% CR)。中位无进展生存期(PFS)为2.6个月(95%置信区间[CI],2.0-3.8个月),中位总生存期(OS)为7.8个月(95% CI,6.2-11.0个月)。6个月PFS为36%(95% CI,30-44),6个月OS为60%(95% CI,54-67)。不符合临床试验入组条件和BsAbs前CD20不可检测均预示更短的PFS和OS。在17例有配对活检的个体中,15例(88.2%)在BsAbs后丢失CD20表达,中位至进展时间为3.7个月。这项纳入R/R DLBCL患者的分析显示,CD3/CD20 BsAbs的ORR与关键临床试验相当,尽管PFS和OS较低。基线CD20不可检测与不良结局相关。这些结果证明了BsAbs在R/R DLBCL中的活性,并强调了靶抗原表达的重要性。
Epcoritamab and glofitamab are CD20-directed bispecific antibodies (BsAbs) approved in the United States for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between 1 January 2023 and 15 October 2024 were collected from 21 United States institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 2.0-3.8 months), and median overall survival (OS) was 7.8 months (95% CI, 6.2-11.0 months). The 6-month PFS was 36% (95% CI, 30-44) and the 6-month OS was 60% (95% CI, 54-67). Both trial ineligibility and undetectable CD20 pre-BsAbs portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after BsAbs with a median time to progression of 3.7 months. This analysis including patients with R/R DLBCL shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 were associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL, and underscore the importance of target antigen expression.
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