CD-19 单核苷酸多态性对 FMC63-CAR-T 细胞疗法治疗结果的临床影响
Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy.
作者信息
Seipel Katja, Abbühl Mariesol, Bacher Ulrike, Nilius Henning, Daskalakis Michael, Pabst Thomas
机构信息
Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland.
Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
出版信息
Cancers (Basel). 2023 Jun 5;15(11):3058. doi: 10.3390/cancers15113058.
Chimeric antigen receptor (CAR)-T cell therapy is effective in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) with response rates of 63-84% and complete response observed in 43-54%. Common germline variants of the target antigen CD19 may elicit different responses to CAR-T cell therapy. The CD19 gene single nucleotide polymorphism rs2904880 encoding leucine or valine at amino acid position 174 of the CD19 antigen was prevalent in 51% of the studied DLBCL patients. In a retrospective comparative analysis of clinical outcome, there were significant differences in CD19 L174 versus V174 carriers: the median time of progression-free survival was 22 vs. 6 months ( = 0.06), overall survival was 37 vs. 8 months ( = 0.11), complete response rates were 51% vs. 30% ( = 0.05), and refractory disease rates were 14% vs. 32% ( = 0.04). The single nucleotide polymorphism in CD19 was shown to influence the treatment outcome in FMC63-anti-CD19-CAR-T cell therapy, and the CD19 minor allele L174 predicted a favorable treatment outcome.
嵌合抗原受体（CAR）-T细胞疗法对复发或难治性弥漫性大B细胞淋巴瘤（r/r DLBCL）患者有效，缓解率为63%-84%，完全缓解率为43%-54%。靶抗原CD19的常见种系变异可能对CAR-T细胞疗法产生不同反应。在51%的研究DLBCL患者中，编码CD19抗原第174位氨基酸亮氨酸或缬氨酸的CD19基因单核苷酸多态性rs2904880普遍存在。在一项临床结局的回顾性比较分析中，CD19 L174携带者与V174携带者存在显著差异：无进展生存期的中位数分别为22个月和6个月（P = 0.06），总生存期分别为37个月和8个月（P = 0.11），完全缓解率分别为51%和30%（P = 0.05），难治性疾病率分别为14%和32%（P = 0.04）。结果表明，CD19中的单核苷酸多态性会影响FMC63-抗CD19-CAR-T细胞疗法的治疗结局，CD19次要等位基因L174预示着良好的治疗结局。
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