抗CD22嵌合抗原受体T细胞疗法作为抗CD19嵌合抗原受体T细胞疗法难治或复发的B细胞恶性肿瘤的挽救治疗方法。
Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy.
作者信息
Zhu Haibo, Deng Haobin, Mu Juan, Lyu Cuicui, Jiang Yanyu, Deng Qi
机构信息
Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, People's Republic of China.
The First Central Clinical College of Tianjin Medical University, Tianjin, People's Republic of China.
出版信息
Onco Targets Ther. 2021 Jul 2;14:4023-4037. doi: 10.2147/OTT.S312904. eCollection 2021.
BACKGROUND
To observe efficacy of the anti-CD22 chimeric antigen receptor modified (anti-CD22-CAR) T cell salvage therapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and B cell acute lymphoid leukemia (B-ALL) patients whose disease did not reach CR or progressed again after anti-CD19-CAR T cell therapy.
METHODS
In our study, seven R/R DLBCL patients reached stable disease (SD) or progression of disease (PD) after their anti-CD19-CAR T cell therapy. Only three in all the six R/R B-ALL patients obtained complete response (CR)/CR with incomplete count recovery (Cri) in their anti-CD19-CAR T cell therapy, but they relapsed again in the following three, six and one months. Then, all these thirteen R/R DLBCL and B-ALL patients received anti-CD22 CAR-T cell salvage therapy because their disease did not reach CR or progressed again.
RESULTS
Four R/R DLBCL patients obtained CR, while two R/R DLBCL patients achieved PR and one patient achieved SD. But only two R/R B-ALL patients obtained Cri in their anti-CD22 CAR-T cell salvage therapy. The overall survival (OS) of R/R DLBCL patients after the anti-CD22 CAR-T cell therapy was 6.142±3.395 months until August 31, 2020. There was no different of the median expansion peaks of the two kinds of CAR T cells (=0.920). The time of anti-CD22-CAR T cell proportion peak days was later than that of the time of anti-CD19-CAR T cell peak days post infusion (=0.022). Their cytokine release syndrome (CRS) was graded 2-4 in their anti-CD19-CAR T cell therapy, while the notable CRS was graded 1-2 in their anti-CD22-CAR T cell therapy. But there was no difference in the CRS and the immune effect or cell associated neurotoxic syndrome (ICANS) grades in the two kinds of therapies. And there was no difference in the hematological toxicity grades in the two kinds of therapies.
CONCLUSION
The anti-CD22-CAR T cell salvage therapy is highly effective in R/R DLBCL patients than in R/R B-ALL patients who failed in anti-CD19-CAR T cell therapy before. We need to expand the number of R/R DLBCL or B-ALL patients and continue to observe.
TRIAL REGISTRATION
ChiCTR-ONN-16009862 and ChiCTR1800019298.
背景
观察抗CD22嵌合抗原受体修饰（anti-CD22-CAR）T细胞挽救疗法对复发/难治性（R/R）弥漫性大B细胞淋巴瘤（DLBCL）及B细胞急性淋巴细胞白血病（B-ALL）患者的疗效，这些患者在接受抗CD19-CAR T细胞治疗后疾病未达完全缓解（CR）或再次进展。
方法
在本研究中，7例R/R DLBCL患者在接受抗CD19-CAR T细胞治疗后病情达到稳定疾病（SD）或疾病进展（PD）。6例R/R B-ALL患者中仅有3例在抗CD19-CAR T细胞治疗中获得完全缓解（CR）/血细胞计数未完全恢复的完全缓解（Cri），但分别在接下来的3个月、6个月和1个月后复发。随后，这13例R/R DLBCL和B-ALL患者均接受了anti-CD22 CAR-T细胞挽救疗法，因为他们的疾病未达CR或再次进展。
结果
4例R/R DLBCL患者获得CR，2例R/R DLBCL患者达到部分缓解（PR），1例患者达到SD。但在anti-CD22 CAR-T细胞挽救疗法中，仅有2例R/R B-ALL患者获得Cri。截至2020年8月31日，R/R DLBCL患者接受anti-CD22 CAR-T细胞治疗后的总生存期（OS）为6.142±3.395个月。两种CAR T细胞的中位扩增峰值无差异（=0.920）。anti-CD22-CAR T细胞比例达到峰值的时间晚于输注后anti-CD19-CAR T细胞达到峰值的时间（=0.022）。他们在抗CD19-CAR T细胞治疗中的细胞因子释放综合征（CRS）分级为2-4级，而在anti-CD22-CAR T细胞治疗中显著的CRS分级为1-2级。但两种疗法在CRS、免疫效应或细胞相关神经毒性综合征（ICANS）分级方面无差异。两种疗法在血液学毒性分级方面也无差异。
结论
对于之前抗CD19-CAR T细胞治疗失败的R/R DLBCL患者，anti-CD22-CAR T细胞挽救疗法比R/R B-ALL患者更有效。我们需要扩大R/R DLBCL或B-ALL患者数量并继续观察。
试验注册
ChiCTR-ONN-16009862和ChiCTR1800019298。
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