Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Ann Med. 2023 Dec;55(1):2230888. doi: 10.1080/07853890.2023.2230888.
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 CD3CD8 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.
嵌合抗原受体（CAR）T 细胞治疗抗 CD19 在复发/难治性（R/R）B 细胞急性淋巴细胞白血病（ALL）患者中显示出优异的疗效。但许多患者对抗 CD19-CAR T 细胞治疗无反应或在 CAR-T 细胞治疗后再次复发。
5 例 R/R B-ALL 患者对抗 CD19-CAR T 细胞治疗无反应或 CAR-T 细胞治疗后再次进展。他们接受了 Blinatumomab 的挽救治疗。观察 Blinatumomab 挽救治疗的临床反应、ALL 细胞上的 CD19 表达、CD3 T 细胞的比例、白细胞介素 6（IL-6）细胞因子水平、血液学毒性、细胞因子释放综合征（CRS）分级和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 高表达的患者中，另 1 例患者在 Blinatumomab 治疗后未获得 NR。在接受 Blinatumomab 治疗后获得 PR 的 Pt5 中，ALL 细胞上的 CD19 表达、CD3 T 细胞和 CD3CD8 T 细胞均缺失。1 例患者（Pt3）被诊断为血液学毒性 0 级。其他 4 例患者被诊断为血液学毒性 2-3 级。CRS 为 0/1 例，1/3 例，2/1 例。ICANS 为 4 例 0 级，1 例 1 级。在 Blinatumomab 治疗期间，2 例患者的毛霉菌肺炎和隐球菌性脑膜脑炎得到控制。
即使在 B-ALL 细胞中 CD19 高表达的 R/R B-ALL 患者、中枢神经系统白血病或合并感染的患者中，Blinatumomab 也可能是抗 CD19-CAR T 治疗后复发/进展的 R/R B-ALL 患者的有效且安全的挽救治疗方法。
