CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T-cell product JCAR017 (TRANSCEND NHL 001).

作者：Jeremy S. Abramson, Maria Lia Palomba, Leo I. Gordon, Matthew A. Lunning, Jon Arnason, Andres Forero‐Torres, Michael Wang, Tina Albertson, Tara S. Allen, Claire L. Sutherland, Benhuai Xie, Jacob Garcia, Tanya Siddiqi · 发表于：Journal of Clinical Oncology · 年份：2017 · DOI：10.1200/jco.2017.35.15_suppl.7513 · 被引用次数：27 · 研究领域：CAR-T cell therapy research、Biosimilars and Bioanalytical Methods

7513 Background: JCAR017 is a second-generation, CD19-directed, 4-1BB CAR T cell product comprising CD8 and CD4 CAR T cells in a 1:1 ratio. A multicenter phase 1 trial of JCAR017 in R/R B-cell NHL (NCT02631044) is underway. Methods: Patients with R/R DLBCL, PMBCL, FL grade 3B, or MCL and adequate organ function are eligible. There was no minimum ALC requirement for apheresis; no test expansion was required. Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by JCAR017. Multiple dose levels (DLs)/administration schedules of JCAR017 are being evaluated. Study objectives include safety, PK, and antitumor response. Results: As of November 23, 2016, 28 patients have been treated and are evaluable for safety and efficacy. Nineteen were male, 9 female; 25 DLBCL, 2 MCL, and 1 FL grade 3B. Median age was 63 years (range 37-79), median number of prior therapies was 4 (range 1-8), 23 (82%) were refractory to their last chemotherapy, and 16 (57%) had prior transplant. No severe cytokine release syndrome (sCRS) was observed; 10 patients had grade 1-2 CRS (1 received tocilizumab). Five patients developed neurotoxicity, including 4 grade 3-4; all events resolved in the 4 patients who had adequate follow up. Median onset of CRS and neurotoxicity were 5 and 11 days, respectively. Four deaths after disease progression occurred, none related to JCAR017. In 20 patients treated at DL1 (5×107 cells), the RR was 80% with 60% achieving CR. One patient with secondary C...