Interventions and outcomes of adult patients with B-ALL progressing after CD19 chimeric antigen receptor T-cell therapy

嵌合抗原受体 Blinatumoab公司 医学 内科学 CD19 挽救疗法 肿瘤科 免疫疗法 免疫学 细胞疗法 抗原 化疗 干细胞 癌症 生物 遗传学
作者
Kitsada Wudhikarn,Jessica Flynn,Isabelle Rivière,Mithat Gönen,Xiuyan Wang,Brigitte Sénéchal,Kevin J. Curran,Mikhail Roshal,P. Maslak,Mark B. Geyer,Elizabeth Halton,Claudia Diamonte,Marco L. Davila,Michel Sadelain,Renier J. Brentjens,Jae H. Park
出处
期刊:Blood [Elsevier BV]
卷期号:138 (7): 531-543 被引量:37
标识
DOI:10.1182/blood.2020009515
摘要

Abstract CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a breakthrough treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, despite the high initial response rate, the majority of adult patients with B-ALL progress after CD19 CAR T-cell therapy. Data on the natural history, management, and outcome of adult B-ALL progressing after CD19 CAR T cells have not been described in detail. Herein, we report comprehensive data of 38 adult patients with B-ALL who progressed after CD19 CAR T therapy at our institution. The median time to progression after CAR T-cell therapy was 5.5 months. Median survival after post–CAR T progression was 7.5 months. A high disease burden at the time of CAR T-cell infusion was significantly associated with risk of post–CAR T progression. Thirty patients (79%) received salvage treatment of post–CAR T disease progression, and 13 patients (43%) achieved complete remission (CR), but remission duration was short. Notably, 7 (58.3%) of 12 patients achieved CR after blinatumomab and/or inotuzumab administered following post–CAR T failure. Multivariate analysis revealed that a longer remission duration from CAR T cells was associated with superior survival after progression following CAR T-cell therapy. In summary, overall prognosis of adult B-ALL patients progressing after CD19 CAR T cells was poor, although a subset of patients achieved sustained remissions to salvage treatments, including blinatumomab, inotuzumab, and reinfusion of CAR T cells. Novel therapeutic strategies are needed to reduce risk of progression after CAR T-cell therapy and improve outcomes of these patients.
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