Efficacy and Safety of Relmacabtagene Autoleucel in Adults with Relapsed/Refractory Follicular Lymphoma in China

Background：Most patients with relapsed/refractory follicular lymphoma (r/r FL) remain incurable and eventually relapse or progress. Previously, initial findings of the pivotal Phase 2 RELIANCE study (NCT04089215) demonstrated a high response rate and low rate of chimeric antigen receptor (CAR) T‐associated toxicity with relmacabtagene autoleucel (relma‐cel) treatment in heavily pretreated patients with r/r FL. Here we present the 6‐month follow‐up results of efficacy, safety, and pharmacokinetics (PK). Methods：Eligible patients with r/r FL had histologically confirmed follicular lymphoma grade (Gr) 1, 2, or 3a, with relapsed/refractory disease after ≥2 prior lines of therapies containing anthracycline and anti‐CD20 agents (e.g. rituximab) or auto‐HSCT. Patients were randomized to receive a single intravenous infusion of autologous CAR+T cells at a dose of 100×106 or 150×106, following lymphodepletion chemotherapy (fludarabine 25 mg/m2 & cyclophosphamide 250 mg/m2 daily×3 days). Patients were evaluated for efficacy (Lugano criteria, 2014), safety (cytokine release syndrome [CRS] by Lee 2014, and all other events by CTCAE v4.03,) and PK (quantitative polymerase chain reaction [qPCR]). The primary endpoint was 3‐month complete response rate (CRR). Key secondary endpoints included 3‐month objective response rate (ORR), duration of response (DOR), progression‐free survival (PFS), overall survival (OS), treatment‐emergent adverse event (TEAE) profile, and PK. Results: At data cut‐off (Dec 17, 2021), 28 patients were enrolled and all completed 6‐month follow‐up. Among them, 16 patients received relma‐cel of 100×106 CAR+ T cells, and 12 patients received 150×106 CAR+ T cells. The median age was 54.0 years (range, 36‐71) and 50% were male. 21 patients (75.0%) had ECOG 0. Histology included FL Gr 1 (n=1), Gr 2 (n=13), Gr 3a (n=10), not specified (n=4). 11 patients (39.3%) had a high tumor burden with SPD >5000 mm2. 10 patients (35.7%) had FLIPI2 scores ≥3. 17 patients (60.7%) had received ≥3 lines of prior therapies. 18 patients were refractory to and 22 patients had relapsed from prior therapy. 9 patients received bridging chemotherapy. Among the 27 efficacy evaluable patients (1 patient was excluded from mITT due to the co‐occurrence of hypofractionated adenocarcinoma of the stomach), the primary endpoint 3‐month CRR was 85.19% (95% confidence interval [CI], 66.27‐95.81). 3‐month ORR was 100% (95% CI, 87.23‐100.00). At the 6‐month follow‐up, 92.59% of patients (95%CI, 75.71‐99.09) were in response with 77.78% of patients (95%CI, 57.74‐91.38) in complete response. At data cut‐off, the best ORR achieved was 100% (95%CI, 87.23‐100.00) with CRR of 92.59% (95%CI, 75.71‐99.09). With a median follow‐up of 11.7 months, median DOR, PFS, and OS have not been reached. 6‐month PFS and OS rates were 95.7% and 100%, respectively. Responses were similar across 100×106 and 150×106 dose groups, as shown in the table. Of 28 treated patients, 18 (64.3%) patients had Gr ≥3 TEAEs, the most common were neutropenia (39.3%), leukopenia (25.0%), and lymphopenia (17.9%). The incidence of CRS and neurotoxicity (NT) was 42.9% and 17.9%, respectively. The median time to CRS onset was 7 days (range, 5‐9) with a median duration of 5 days (range, 2‐7). No Gr ≥3 CRS was observed. The median time to NT onset was 9 days (range, 4‐9) with a median duration of 7 days (range, 2‐25). Only 1 patient experienced Gr ≥3 NT. To manage CRS and/or NT, 5 patients received tocilizumab or corticosteroids. No deaths occurred. qPCR assay showed that the CAR transgene was firstly detectable from Day 4 to 15 after infusion, and time to peak CAR‐T cell expansion was 7 to 23 days. 7 patients still had CAR‐T detectable on Day 180. The table presented similar safety profiles and PK characteristics across 100×106 and 150×106 dose groups. Conclusions: With 11.7 months of median follow‐up, relma‐cel demonstrated remarkable clinical responses achieving high rates of CR and OR, and a manageable safety profile in the phase 2 study of CAR T cell therapy in r/r FL. Updated safety and efficacy data with a longer follow‐up will be presented. [Formula presented] Disclosures: Tian: JW Therapeutics: Current Employment. Huang: JW Therapeutics: Current Employment. Zhou: JW Therapeutics: Current Employment. Ma: JW Therapeutics: Current Employment. Yang: JW Therapeutics: Current Employment. Qin: JW Therapeutics: Current Employment.