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:Blinatumomab as salvage therapy in patients with relapsed/refractory B-ALL who have failed/progressed after anti-CD19-CAR T therapy.
Blinatumomab as salvage therapy in patients with relapsed/refractory B-ALL who have failed/progressed after anti-CD19-CAR T therapy.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
抗CD19嵌合抗原受体(CAR)T细胞疗法已被证明在复发/难治性(R/R)B细胞急性淋巴细胞白血病(ALL)患者中具有极好的疗效。但许多患者对anti-CD19-CAR-T 细胞疗法无效或再次复发。
5例R/R B-ALL患者对anti-CD19-CAR-T 细胞治疗无应答或在CAR-T 细胞治疗后再次出现疾病进展。他们接受了Blinatumomab的挽救治疗。在Blinatumomab挽救治疗中,观察了临床反应、ALL细胞上CD19的表达、CD3+ T细胞比例、白细胞介素-6(IL-6)的细胞因子水平、血液学毒性、细胞因子释放综合征(CRS)分级以及免疫效应细胞相关神经毒性综合征(ICANS)。
4例患者获得CR/CRi,即使在B-ALL细胞中CD19不高表达的患者中也是如此,而另1例患者在Blinatumomab治疗后获得NR。在获得Blinatumomab治疗PR的Pt 5中,ALL细胞上的CD19表达、CD3 + T细胞比例和CD3 + CD8 + T细胞均不足。1例患者(Pt 3)被诊断为0级血液学毒性。其他4例患者被诊断为2-3级血液学毒性。CRS为0级/1例患者,1级/3例,2级/1例。ICANS为0级/4例患者,1级/1例。2例患者的Rhizopus microsporus肺炎和隐球菌脑病在Blinatumomab治疗期间得到控制。
Blinatumomab 可能是对 anti-CD19-CAR-T 治疗后失败/进展的 R/R B-ALL 患者有效且安全的挽救治疗,即使在 B-ALL 细胞中 CD19 未高表达的 R/R B-ALL 患者、伴有 CNS 白血病或合并感染的患者中也是如此。关键信息部分 R/R B-ALL 患者对抗 anti-CD19 CAR-T 细胞治疗无反应或再次出现疾病进展。对此类患者有效且安全的挽救治疗仍有待探索。Blinatumomab 可能是对 anti-CD19-CAR-T 治疗后失败/进展的 R/R B-ALL 患者有效且安全的挽救治疗,即使在 B-ALL 细胞中 CD19 未高表达的患者中也是如此。Blinatumomab 可能是对 anti-CD19-CAR-T 治疗后失败/进展的 R/R B-ALL 患者有效且安全的挽救治疗,即使在伴有 CNS 白血病或合并感染的患者中也是如此。
Anti-CD19 chimeric antigen receptors (CARs) T-cell therapy has been shown to have excellent efficacy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). But many patients are refractory to anti-CD19-CAR T-cell therapy or relapse again.
Five patients with R/R B-ALL did not respond to anti-CD19-CAR T-cell therapy or had a disease progression again after CAR-T cell therapy. They received a salvage therapy of Blinatumomab. The clinical response, CD19 expression on ALL cells, the proportion of CD3 + T cells, level of cytokine levels of interleukin-6 (IL-6), hematological toxicity, grade of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxic syndrome (ICANS) were observed in salvage therapy of Blinatumomab.
Four patients obtained CR/CRi, even in patients without high expression of CD19 in B-ALL cells, while the other patient received NR after Blinatumomab therapy. The CD19 expression on ALL cells, the proportion of CD3 + T cells, and CD3 + CD8 + T cells were deficient in Pt 5, who obtained PR in Blinatumomab therapy. One patient (Pt 3) was diagnosed with grade 0 hematological toxicity. The other four patients were diagnosed with grades 2-3 of hematological toxicity. The CRS was grade 0/one patient, grade 1/three, and grade 2/one. The ICANS was grade 0/four patients, grade 1/one. Rhizopus microsporus pneumonia and cryptococcal encephalopathy in two patients were controlled during Blinatumomab therapy.
Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in R/R B-ALL patients without high expression of CD19 in B-ALL cells, patients with CNS leukemia or co-infection.Key messagesSome R/R B-ALL patients did not respond to anti-CD19 CAR T-cell therapy or had a disease progression again. Effective and safe salvage therapy for such patients remains to be explored.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients without high expression of CD19 in B-ALL cells.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients with CNS leukemia or co-infection.
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