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:Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma.
Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma.
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大B细胞淋巴瘤患者在二线(2L)CAR-T 细胞治疗后进展,可选择的CAR-T 后治疗方案日益增多,若存在CAR-T 失败高风险,应考虑及时干预。在这项纳入302例接受2L axicabtagene ciloleucel(axi-cel)治疗患者的全国性队列中,我们评估了早期氟脱氧葡萄糖正电子发射断层扫描(PET)反应在指导CAR-T 后管理中的应用。共有245例在1个月时有治疗反应的患者,根据Deauville评分(DS)按缓解深度分组:完全代谢缓解或桥接放疗野内局灶性残留活性(DS1-3/DS4RT)、部分缓解(PR)DS4和PR DS5。DS反应类别与进展风险、无进展生存期和总生存期显著相关。DS4和DS5反应患者至第6个月时的进展风险分别为50%和73%,而DS1-3/DS4RT为25%(DS4:风险比[HR],3.07 [95% CI:1.85-5.07];DS5:HR,5.20 [95% CI:2.95-9.16];P< .0001),这在多变量分析中具有独立显著性。在使用DS类别和输注前乳酸脱氢酶水平2倍正常上限的风险模型中,我们识别出一个具有显著早期失败风险的高危组(HR,5.21 [95% CI:3.27-8.29];P< .001)。
我们的结果证明,早期PET反应在接受2L axi-cel治疗的患者中具有预后价值,且独立于输注前风险因素。有反应的高危患者至第6个月时进展风险为70%,应强烈考虑尽早接受CAR-T 后治疗。
Patients with large B-cell lymphoma who progress after second-line (2L) chimeric antigen receptor T cell (CAR T) therapy have an increasing number of post-CAR T treatment options available and should be considered for timely intervention if at high risk of CAR T failure. In this national cohort of 302 patients receiving 2L axicabtagene ciloleucel (axi-cel), we assessed the use of early fluorodeoxyglucose positron emission tomography (PET) response to guide post-CAR T management. A total of 245 patients with treatment response at 1 month were grouped according to depth of response by Deauville score (DS): complete metabolic response or focal residual activity in the bridging radiotherapy field (DS1-3/DS4RT), partial response (PR) DS4, and PR DS5.
DS response categories were significantly associated with risk of progression, progression-free survival, and overall survival. Patients with DS4 and DS5 response had a 50% and 73% risk of progression by month 6, respectively, compared with 25% for DS1-3/DS4RT (DS4: hazard ratio [HR], 3. 07 [95% CI: 1. 85-5. 07] and DS5: HR, 5.
20 [95% CI: 2. 95-9. 16]; P< . 0001), which was independently significant in multivariable analyses. In a risk model using DS categories and preinfusion lactate dehydrogenase levels 2 upper limit of normal, we identified a high-risk group with significant risk of early failure (HR, 5. 21 [95% CI: 3. 27-8. 29]; P< . 001).
Our results demonstrate the prognostic value of early PET response in patients treated with 2L axi-cel, independent of preinfusion risk factors. Responding high-risk patients had 70% risk of progression by month 6 and should be strongly considered for early post-CAR T therapies.
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