An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T（CAR-T） cells

• Published in: 中国科学：生命科学英文版 no. 4; pp. 379 - 385
• Main Author: Yajing Zhang Wenying Zhang Hanren Dai Yao Wang Fengxia Shi Chunmeng Wang Yelei Guo Yang Liu Meixia Chen Kaichao Feng Yan Zhang Chuanjie Liu Qingming Yang Suxia Li Weidong Han
• Format: Journal Article
• Language: English
• Published: 2016
• Subjects: CD19; T细胞; 免疫治疗; 受体; 复发; 异基因造血干细胞移植; 患者; 生物标志物
• ISSN: 1674-7305; 1869-1889

Anti-CD19 chimeric antigen receptor-modified T（CAR-T-19） cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines（mainly interleukin 6 and C-reactive protein） were identified in two patients（Nos. 1 and 6） even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.