Decreased Rates of Severe CRS Seen with Early Intervention Strategies for CD19 CAR-T Cell Toxicity Management

作者：Rebecca Gardner, Kasey J. Leger, Colleen Annesley, Corinne Summers, Julie Rivers, Juliane Gust, Katherine Tarlock, Todd M Cooper, Navin Pinto, Olivia Finney, Hannah Smithers, Assaf P. Oron, Daniel Li, Julie R. Park, Michael C. Jensen · 发表于：Blood · 年份：2016 · DOI：10.1182/blood.v128.22.586.586 · 被引用次数：66 · 研究领域：CAR-T cell therapy research、Cell Image Analysis Techniques

Abstract Introduction: CD19 CAR-T cell therapy is a promising strategy in the treatment of pre-B ALL, with early phase trials showing results of >90% CR rates. Over 90% of patients develop CRS concurrent with proliferation of CAR-T cells. Rates of severe CRS (sCRS) in previously reported studies have ranged from 23% to 43%. Concerns have been raised that the use of immunomodulation may impact engraftment and proliferation of CAR-T cells, potentially impairing efficacy. Additionally, concern has been raised that the use of tocilizumab (toci) may lead to an increased risk of neurotoxicity. Here we report our clinical experience with early treatment of CRS in a cohort of patients who received pre-emptive toci and dexamethasone (dex) with the goal to lessen the occurrence of sCRS. Methods: Subjects enrolled on the PLAT-02 study (NCT02028455) underwent apheresis and CAR-T cell manufacturing followed by lymphodepletion and CAR-T cell infusion. In this phase 1 dose escalation study, subjects were treated from 0.5- 10 x 106 CAR T cells/kg. sCRS included the use of pressors or inotropes. Severe neurotoxicity included any grade 3/4 neurotoxicity, excluding headache, and grade≥ 2 seizure. The first 23 subjects received toci (8mg/kg) with or without steroids for dose limiting toxicity (DLT). Subsequently the protocol was modified to provide guidelines for early intervention with CRS. The next 20 subjects received toci and subsequent dex (5-10mg every 6-12 hours prn) for persistent sympto...