CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Outcome after chimeric antigen receptor (CAR) T-cell therapy failure in large B-cell lymphomas.
Outcome after chimeric antigen receptor (CAR) T-cell therapy failure in large B-cell lymphomas.
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背景:大B细胞淋巴瘤(LBCL)患者接受CAR-T 细胞治疗后若复发或难治,后续治疗选择有限,预后较差。本回顾性研究纳入51例CAR-T 治疗失败的LBCL患者,其中22例参加临床试验,29例接受标准治疗或支持治疗。39例接受了后续抗肿瘤治疗,其中26例接受免疫治疗。中位随访时间为11.7个月,12个月总生存率为35%。较高的循环肿瘤DNA水平与较差结局相关;多变量分析显示,后续治疗无应答(风险比3.08,p=0.0109)以及原诊断并非原发性纵隔大B细胞淋巴瘤或转化滤泡性淋巴瘤(风险比4.54,p=0.0069)与更差生存相关。研究显示,CAR-T 治疗失败后的预后仍然不佳,亟需更有效的挽救治疗。
This study retrospectively evaluated the outcome of salvage therapy in 51 patients who failed axicabtagene ciloleucel or tisagenlecleucel for relapsed/refractory large B-cell lymphomas. Of these patients, 22 (43%) were enrolled in clinical trials (glofitamab or loncastuximab tesirine + ibrutinib), whereas 29 received standard therapies (lenalidomide [Len], checkpoint inhibitors [CPIs], ibrutinib [I], chemoimmunotherapy and radiotherapy) or supportive care.
Overall, 26 of 39 (67%) treated patients received a treatment based on immunotherapy (glofitamab, CPI, Len) that was mainly represented by bispecific antibody (n = 18). In this subgroup, plasma samples were collected and analysed for circulating tumour DNA (ctDNA) using cancer-personalized profiling by deep sequencing (CAPP-seq). The study found that patients with high ctDNA had poor outcomes.
At a median follow-up of 11. 7 months, the estimated 12-month overall survival (OS) was 35%. Factors adversely affecting the prognosis in the multivariable model were the absence of response to CAR T-cell therapy (HR: 3. 08; p = 0. 0109) and a diagnosis other than PMBCL and t-FL (HR: 4. 54; p = 0. 0069). The outcome of patients failing CAR T cells is poor and requires further investigation.
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