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:Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration.
Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration.
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我们的发现有助于更好地对 CAR-Tx 候选者进行分层,并强调需要采取积极主动的方法(更早重新分期,在达到部分缓解后进行干预)。
本研究旨在分析接受CAR-T 细胞治疗(CAR-Tx)的大B细胞淋巴瘤(LBCL)患者的结局,重点关注CAR-T 细胞治疗失败后的结局,并明确快速进展和进一步治疗的风险因素。
我们分析了2019年至2022年间在捷克共和国和斯洛伐克接受三线tisagenlecleucel或axicabtagene ciloleucel治疗的107例LBCL患者。
总体缓解率(ORR)为60%,完全缓解(CR)率为50%。中位无进展生存期(PFS)和总生存期(OS)分别为4.3个月和26.4个月。63例患者(59%)在CAR-Tx后难治或复发。在这些患者中,39例接受了放疗或全身治疗,ORR为22%(CR 8%)。治疗失败后存活患者的中位随访时间为10.6个月。甚至在CAR-Tx之前就已存在若干预测后续治疗实施和结局的因素。CAR-Tx失败后未接受进一步治疗的危险因素包括:单采前高乳酸脱氢酶(LDH)水平、结外受累(EN)、淋巴细胞清除(LD)前高铁蛋白水平以及R/P时ECOG PS >1。接受治疗患者的中位OS-2(自CAR-Tx后R/P起)为6.7个月(6个月57.9%),未接受治疗患者为0.4个月(6个月4.2%)(p < 0.001)。接受治疗患者的中位PFS-2(自CAR-Tx后R/P起)为3.2个月(6个月28.5%)。较短PFS-2(n = 39)的危险因素包括:LD前CRP > 正常范围上限(LNR)、白蛋白 < LNR以及R/P时ECOG PS > 1。所有这些因素,连同LD前LDH > LNR和R/P时EN受累,均可预测接受治疗患者的OS-2。
We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in 3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022.
The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty-three patients (59%) were refractory or relapsed after CAR-Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow-up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR-Tx. Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001). The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients. The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients.
Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).
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