• 111例r-NHL患者参与Axi-cel治疗实验,101例修订的意向分析集人群;
  • 43例接受tocilizumab治疗,27例接受类固醇以缓解CRS ;
  • 84%神经不良反应(NE),ORR为 78%;
  • ≥3级AE:66%中性粒细胞减少症、44%白细胞减少、43%贫血、31%发热性中性粒细胞减少、24%血小板减少、21%脑病,≥3级CRS和NE分别为13%和28%,3例>5级AE;
  • Axi-cel治疗r-NHL,ORR=82%,中位随访时间8.7个月44%保持缓解,AE可控,且tocilizumab /类固醇的使用并未影响其疗效。

Clinical and biologic covariates of outcomes in ZUMA-1: A pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (r-NHL)

ZUMA-1临床和生物学因素结果:一个axicabtagene ciloleucel (axi-cel; KTE-C19)治疗难治性侵袭性非霍奇金淋巴瘤(r-nhl)的关键实验


Abstract & Authors:展开

Background: Outcomes in activated B cell subtype diffuse large B cell lymphoma (ABC-DLBCL) and r-NHL are poor (Sehn Blood 2015, Crump ASCO 2016). ZUMA-1 is the first, multicenter trial of anti-CD19 chimeric antigen receptor (CAR) T cells, axi-cel, in r-NHL.
Methods: Dosing and eligibility were per Neelapu ASH 2016. The primary endpoint was objective response rate (ORR); secondary endpoints were duration of response (DOR), overall survival (OS), and safety. Cell of origin (COO) and CD19 status were assessed centrally using Lymphoma Subtyping Test NanoString (Wallden JCO 2015) and a validated immunohistochemistry assay, respectively.
Results: As of Jan 27, 2017, 111 patients (pts) were enrolled; the manufacturing success rate was 99% with an average 17-d turnaround time; 101 pts (modified intent-to-treat [mITT] population) received axi-cel. In the mITT population, the ORR was 82% (complete response [CR], 54%). With 8.7 m median follow-up, 44% remain in response and 39% in CR. The median DOR was 8.1 m and not reached (NR) for pts with CR. Median OS was NR. Results for clinical and biologic covariates are listed in the table. In pts who received tocilizumab (n = 43) and/or steroids (n = 27) for cytokine release syndrome (CRS) and/or neurologic events (NE), ORR was 84% and 78%, respectively. Most common grade ≥3 adverse events (AEs) were neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), thrombocytopenia (24%), and encephalopathy (21%). Rates of grade ≥3 CRS and NE were 13% and 28%, respectively. There were 3 grade 5 AEs (Neelapu ASH 2016).
Conclusions: Axi-cel induced an ORR of 82% in pts with r-NHL, response is ongoing in 44% of pts at 8.7 m. Similar clinical responses were observed in pts with r-ABC-DLBCL. AEs were manageable and the use of tocilizumab/steroids did not appear to impact ORR. Drs Locke and Neelapu contributed equally.

All Authors:
Frederick Lundry Locke