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:Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers.
共识别出173例患者为DR/INT。
基于抗PD-1的疗法和brentuximab vedotin (BV)已显著改善经典霍奇金淋巴瘤(cHL)患者的生存,并已被纳入更早期的治疗线。然而,关于出现难治性疾病或对BV和抗PD-1疗法不耐受(双重难治/不耐受;DR/INT)患者的临床结局,目前数据不足。在此,我们评估了来自15个美国学术医学中心的DR/INT cHL患者的结局。共识别出173例DR/INT患者。自cHL诊断时起的中位总生存期(OS-1)为14.8年(95% CI:10.9-20.9年),10年OS-1估计值为62%(95% CI:52-70%)。在考虑年龄差异后,在发生DR/INT之前接受过自体干细胞移植的患者OS-1显著更长(HR 0.53,95% CI:0.29-0.96,p = 0.04)。自DR/INT时起的中位OS(OS-2)为7.4年(95% CI:4.3-NR),5年OS-2估计值为57%(95% CI:48-66%)。基于抗PD-1和BV的疗法再挑战均有效,中位PFS分别为237天(95% CI:155-357天)和183天(95% CI:108-273天)。最后,DR/INT后的先进治疗选择,如CD30靶向CAR-T 细胞疗法和异基因干细胞移植,与OS-2改善相关(p < 0.001)。据我们所知,这是最大的DR/INT cHL患者队列。OS-2将作为未来旨在改善DR/INT cHL生存的研究的基准。
Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop refractory disease or who become intolerant of BV and anti-PD-1 therapies (double refractory/intolerant; DR/INT). Here, we evaluated outcomes in patients with DR/INT cHL from 15 US academic medical centers. A total of 173 patients were identified as DR/INT. The median overall survival from the time of cHL diagnosis (OS-1) was 14.8 years (95% CI: 10.9-20.9 years) and the 10-year OS-1 estimate was 62% (95% CI: 52-70%). After accounting for differences in age, patients who underwent autologous stem cell transplant prior to developing DR/INT had significantly longer OS-1 (HR 0.53, 95% CI: 0.29-0.96, p = 0.04). Median OS from time of DR/INT (OS-2) was 7.4 years (95% CI: 4.3-NR) and the 5-year OS-2 estimate was 57% (95% CI: 48-66%). Both anti-PD-1 and BV based therapy rechallenge were effective with median PFS of 237 days (95% CI: 155-357 days) and 183 days (95% CI: 108-273 days), respectively. Finally, advanced therapy options such as CD30 directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after DR/INT were associated with improved OS-2 (p < 0.001). To our knowledge, this represents the largest cohort of patients with DR/INT cHL. OS-2 will serve as a benchmark for future studies aiming to improve survival in DR/INT cHL.
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