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:CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma.
CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma.
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复发和/或难治性(R/R)滤泡性淋巴瘤(FL)和套细胞淋巴瘤(MCL)患者预后较差,预计无进展生存期和总生存期较短。美国已批准两种靶向CD19的CAR-T 细胞疗法用于R/R FL,即axicabtagene ciloleucel(axi-cel)和tisagenlecleucel。ZUMA-5和ELARA研究的结果分别促成了axi-cel和tisagenlecleucel的获批,这两项研究在既往分别接受过中位3线(范围=2-4)和4线(范围=2-13)治疗的高危FL患者人群中展示了较高的总缓解率(ORR)和完全缓解(CR)率。例如,ZUMA-5的ORR为94%(CR=79%),ELARA的ORR为86%(CR=69.1%)。关于MCL,基于ZUMA-2研究的结果,brexucabtagene autoleucel获批用于R/R MCL。在后一项研究中,尽管所有R/R MCL患者均曾暴露于Bruton酪氨酸激酶抑制剂,报告的ORR为91%,其中68%达到CR。这些结果无疑证明了CAR-T 疗法在R/R FL和MCL中均有较强疗效;然而,必须承认上述所有研究的随访时间相对较短。
因此,绝对需要更长时间的随访以显示缓解的持久性和长期安全性。
Patients with relapsed and/or refractory (R/R) follicular lymphoma (FL) and mantle cell lymphoma (MCL) have a poor prognosis with anticipated short progression-free and overall survivals. Two CD19-directed chimeric antigen receptor T-cell (CAR T) therapies are approved in the United States for R/R FL, namely, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel. The results of ZUMA-5 and ELARA studies led to the approval of axi-cel and tisagenlecleucel, respectively, after demonstrating high overall (ORR) and complete response (CR) rates in this high-risk population of FL patients who had received a median of 3 (range = 2-4) and 4 (range = 2-13) prior lines of therapies, respectively.
For instance, the ORR for ZUMA-5 was 94% (CR = 79%), and for ELARA, it was 86% (CR = 69. 1%). Pertaining to MCL, brexucabtagene autoleucel is approved for R/R MCL based on results of the ZUMA-2 study.
In the latter study, despite the fact that all R/R MCL patients had been exposed to prior Bruton's tyrosine kinase inhibitors, the reported ORR was 91%, with 68% achieving a CR. These results undoubtedly demonstrate a strong efficacy of CAR T therapy in both R/R FL and MCL; yet, one must acknowledge the relatively short follow-up time of all aforementioned studies.
Thus, longer follow-up showing durability of responses and long-term safety is definitely needed.
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