在复发或难治性B细胞恶性肿瘤患者中,CD22和CD19双靶向嵌合抗原受体T细胞治疗的疗效和安全性:一项荟萃分析。
Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis.
发表日期:2023 Sep 05
作者:
Thi Thuy Nguyen, Nguyen Thanh Nhu, Chia-Ling Chen, Chiou-Feng Lin
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
观察了CD22或CD19嵌合抗原受体T(CAR-T)细胞在急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤(NHL)治疗中的疗效。由于抗原丧失和CAR-T细胞持续性不足是单一抗原靶向治疗后疾病进展的主要原因,我们评估了CD22 / CD19双靶向CAR-T细胞疗法在复发/难治性B细胞恶性肿瘤中的疗效和安全性。我们在Web of Science,PubMed,Cochrane和Embase数据库中搜索了截至2022年7月的文献。纳入了任何复发/难治性B细胞血液恶性肿瘤的确诊患者,无论年龄,性别或种族,接受CD22和CD19双靶向CAR-T细胞疗法。排除了与其他癌症共存的患者的研究。我们使用随机效应模型探索结果,并通过亚组分析调查异质性四个研究(405名患者)被纳入。对于所有患者,整体应答率(OR)和完全缓解(CR)分别为97%和93%。总生存率(OS)和无进展生存率(PFS)的1年比例分别为70%和49%。对于NHL,OR发生在85%的患者中,57%的患者经历了CR。结果表明,1年生存率(OS)和1年无进展生存率(PFS)分别为77%和65%。亚组分析显示,在以下情况下,双靶向模式在以下情况下实现了更高的CR:联合应用CD22 / CD19-CAR-T细胞和第三代CAR-T细胞,并结合ASCT和BEAM预处理。对于治疗相关毒性,ALL和NHL组似乎相似:86%,7%和12%的患者分别出现了所有级别的细胞因子释放综合征(CRS),严重CRS和神经毒性。我们的荟萃分析证明,CD22 / CD19双靶向CAR-T细胞策略在B细胞恶性肿瘤中具有高效性和可接受的不良反应。© 2023 Wiley & Sons Ltd. 发表于《癌症医学》的作者。
The efficacy of CD22 or CD19 chimeric antigen receptor T (CAR-T) cells in the management of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) was observed. Because antigen loss and lack of CAR-T-cell persistence are the leading causes of progressive disease following single-antigen targeting, we evaluated CD22/CD19 dual-targeting CAR-T-cell therapy efficacy and safety in relapsed/refractory B-cell malignancies.The Web of Science, PubMed, Cochrane, and Embase databases were searched until July 2022. Patients confirmed with any relapsed/refractory B-cell hematological malignancies were included regardless of age, gender, or ethnicity, receiving CD22 and CD19-dual-targeting CAR-T-cell therapy. The studies conducted on patients with coexisting other cancer were excluded. We used random-effect models to explore the outcome, and heterogeneity was investigated by subgroup analysis.Fourteen studies (405 patients) were included. The pooled overall response (OR) and complete remission (CR) were 97% and 93%, respectively, for ALL patients. The 1-year proportions of overall survival (OS) and progression-free survival (PFS) were 70% and 49%, respectively. For NHL, OR occurred in 85% of patients, and 57% experienced CR. The results illustrated that the 1-year OS and 1-year PFS were 77% and 65%, respectively. The subgroup analysis showed that the dual-targeting modality achieved higher CR in the following cases: coadministration of CD22/CD19-CAR-T cells and third-generation CAR-T cells combined with ASCT and BEAM pretreatment. The ALL and NHL groups seemed similar in treatment-related toxicity: all grade cytokine release syndrome (CRS), severe CRS, and neurotoxicity occurred in 86%, 7%, and 12% of patients, respectively.Our meta-analysis demonstrated that the CD22/CD19 dual-targeting CAR-T-cell strategy has high efficiency with tolerable adverse effects in B-cell malignancies.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.