Two-year follow-up result of RELIANCE study, a multicenter phase 2 trial of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma.
Authors: Ying Zhitao , Song Yuqin , Yang Haiyan , Guo Ye , Li Wenyu , Zou Dehui , Zhou Daobin , Wang Zhao , Zhang Mingzhi , Wu Jianqiu , Liu Hui , Wang Chris , Yang Su , Zhou Zisong , Qin Yun , Zhu Jun 
Published: June 2022

7529

Background: RELIANCE study is the first pivotal CD19 CAR-T study that got IND approval by the authority in China (NCT04089215). Initial findings of this study demonstrated high response rates and low rates of CAR-T–associated toxicity with Relmacabtagene autoleucel (Carteyva, also known as Relma-cel, JWCAR029) treatment in heavily pretreated patients with Relapsed/Refractory (r/r) large B-cell lymphoma (LBCL) (Ying et al. Cancer Med, 2020). Here we provide 2-year follow-up result of RELIANCE study. Methods: 59 adults (age ≥18 years) with ≥2 prior therapies r/r LBCL were randomized to receive lymphodepletion chemotherapy followed by a single infusion of Carteyva at a dose of 100×106 or 150×106 CAR+T cells, patients were evaluated for efficacy using Lugano criteria (Cheson 2014), for toxicity using CTCAE v4.03 and for cytokine release syndrome (CRS) using Lee et al. criteria (Blood 2014). Primary endpoint was 3-month objective response rate (ORR); key secondary endpoints included complete response rate (CRR) at 3 months, duration of response (DOR), progression-free survival (PFS), overall survival (OS) and treatment-emergent adverse event (TEAE) profile. Results: The cutoff date was December 22, 2021. All 59 patients (median age 56.0 years, range 18–75 years) were post-treatment with Carteyva, among of them 26 patients completed trial, 8 patients on study, 25 patients withdrew. Among the modified intent-to-treat (mITT) population of 58 efficacy-evaluable patients, best ORR and CRR was 77.6% and 53.5%, respectively. The median follow-up was 24 months(95% CI 23.9-24.1), median PFS and DOR was 7 months (95% CI 4.76–24.15) and 20.3 months (95% CI 4.86–NA), median OS was NA (95% CI NA–NA). 2-year PFS, DOR and OS rates were 38.3%, 38.1% and 69.0%, respectively. 91.5% patients reported treatment–related TEAEs with 72.9% patients had Grade ≥3, among this, the most common Grade ≥3 AE were neutropenia (42.4%) and leukopenia (22%). CRS and NT of any grade occurred in 47.5% and 20.3% of patients (Grade 3–4 CRS, 5.1%; Grade 3–4 NT, 3.4%). Median onset of CRS and NT was 4 (1–10) days and 8.5 (2–11) days, After Day 90, 6(10.2%) patients reported AEs Grade ≥3, the most common were lymphocytopenia 2(3.4%), neutropenia 2(3.4%) and leukopenia 1(1.7%). Grade ≥ 3 infections occurred in 2(3.4%) patients, which was gastroenteritis and herpes zoster. 17 (28.8%) patients died in this study, 12(20.3%) due to disease progression. Conclusions: As the longest follow-up term of CD19+ CAR T cell study in heavily pretreated patients with r/r LBCL in China, Carteyva demonstrated durable responses with a high 2-year OS rate, the median OS not yet reached for responding patients, and a manageable safety profile. These data continue supporting the compelling clinical benefit-risk profile of Carteyva for r/r LBCL patients. Clinical trial information: NCT04089215.