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:Meta-analysis of response rates to first-line salvage treatment after CAR-T therapy failure in large B-cell lymphoma patients.
Meta-analysis of response rates to first-line salvage treatment after CAR-T therapy failure in large B-cell lymphoma patients.
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非 CD19 CAR-T 细胞与更高的缓解率相关,若患者符合条件应考虑使用。鉴于各项估计值存在异质性,结果应谨慎解读。
对于接受嵌合抗原受体(CAR)-T治疗后未缓解或复发的LBCL患者,其预后仍然很差,目前对于最有效的挽救方案尚未达成共识。
我们进行了一项随机效应荟萃分析,评估CAR-T 治疗后复发/难治性LBCL一线治疗的完全缓解(CR)率和总缓解率(ORR)。我们遵循了PROSPERO上可获取的预设方案(CRD42023473854)。
我们确定了41项研究,评估了以下干预措施:非CD19 CAR-T、CD19 CAR-T、双特异性抗体(BiTEs)、基于来那度胺和polatuzumab的方案、放疗、免疫检查点抑制剂(ICI)、Bruton酪氨酸激酶抑制剂(BTKi)。非CD19 CAR-T 细胞产生了最佳的CR(56%,CI:40-71%),显著高于除CD19 CAR-T(CR = 30%,CI:7-58%)以外的其他干预措施。BiTEs、放疗、基于来那度胺和polatuzumab的方案(CR分别为:28%、26%、19%、24%)彼此之间无显著差异。ICI和BTKi显示出最低的CR率(分别为12%,CI:5-20%和8%,CI:0-23%),也显著劣于BiTEs。ORR最高的是非CD19 CAR-T(ORR = 80%,CI:66-92%),而所有其他方案的值均低于50%。
We conducted a random-effects meta-analysis of complete response (CR) and overall response rates (ORR) to first-line treatments for CAR-T-relapsed/refractory LBCL. We followed the predefined protocol available at PROSPERO (CRD42023473854).
We identified 41 studies evaluating the following interventions: non-CD19 CAR-T, CD19 CAR-T, bispecific antibodies (BiTEs), lenalidomide- and polatuzumab-based regimens, radiotherapy, immune checkpoint inhibitors (ICI), Bruton's Tyrosine Kinase inhibitors (BTKi). Non-CD19 CAR-T cells yielded the best CR (56%, CI: 40-71%), significantly higher than other interventions except CD19 CAR-T (CR = 30%, CI: 7-58%). BiTEs, radiotherapy, lenalidomide- and polatuzumab-based regimens (CR: 28%, 26%, 19%, 24% respectively) did not differ significantly from each other. ICI and BTKi showed the lowest CR rates (12%, CI: 5-20% and 8%, CI: 0-23%, respectively), and were also significantly inferior to BiTEs. ORR was the highest for non-CD19 CAR-T (ORR = 80%, CI: 66-92%), whereas all other regimens yielded values below 50%.
Non-CD19 CAR-T cells were associated with higher response rates and should be considered if patients are eligible. Given the heterogeneity of the estimates, the results should be interpreted cautiously. REGISTRATION: PROSPERO CRD42023473854.
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