Background: Tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has been approved in the United States and Europe for adults with r/r FL after ≥2 lines of prior therapy based on the phase 2 ELARA trial (NCT03568461) in 2022. With a median follow-up (mFU) of 53 months, 4-year progression-free survival (PFS) was 50.2% along with a favorable safety profile (Thieblemont C, ASH 2024). Here, we report the final analysis from the ELARA trial after mFU of >5 years.

Methods: Eligible patients (pts) with r/r FL (grade 1-3A) previously treated with ≥2 lines of systemic therapy (including an anti-CD20 monoclonal antibody and alkylating agent) received a single tisagenlecleucel infusion (0.6-6 × 108 CAR+ viable T cells). Bridging therapy was permitted. Here, a long-term efficacy and safety analysis, including duration of response (DOR), PFS, and overall survival (OS) in all pts and in pts with high-risk disease characteristics along with safety analysis are reported. Cellular kinetics were determined by the measurement of transgene levels by quantitative polymerase chain reaction.

Results: As of May 28, 2025, mFU was 61.0 months (range: 3.1–67.0 months) in all infused pts (N=97). All pts were evaluable for safety and 94 pts for efficacy. At baseline, pts with high-risk disease characteristics included 60% with high Follicular Lymphoma International Prognostic Index score (FLIPI) of ≥3, 62% with progression of disease within 2 years of frontline systemic therapy (POD24), 64% with bulky disease (>7 cm or 3 lesions >3 cm), 68% with double refractory to prior CD20 antibody and alkylating agent, and 21% with high tumor burden (total metabolic tumor volume >510 mL). The ORR (86.2%) and CR (68.1%) remained consistent with previous data in overall pts and high-risk disease characteristics subgroups (Dreyling M, Blood 2024). The median DOR was not reached (95% confidence internal [CI]: 35.8–NE), the 4-year estimated DOR in all responders was 61% (95% CI, 48.8–71.1) and 71.2% (95% CI, 57.7–81.1) in pts achieving CR. The median PFS was 53.2 months (95% CI,18.2–NE) with an estimated 5-year PFS of 46% (95% CI, 35.0–56.3) in the overall population and 59.8% (95% CI, 46.2–71.1) in pts with CR. In pts with high-risk disease characteristics, 5-year estimated PFS was 35.5% (high FLIPI), 41.1% (POD24), 45.1% (bulky disease), 50.5% (double refractory). In pts with high tumor burden, 5-year PFS was not estimable due to small subgroup size. At this final analysis, median OS was not reached; with an estimated 5-year OS of 74.1% (95% CI, 63.0–82.3). Among identified high-risk pts, estimated 5-year OS was 64.4% (high FLIPI), 74.6% (POD24), 71.1% (bulky disease), 79.8% (double refractory), and 65.5% (high tumor burden). CAR transgene persistence (Tlast; time to last quantifiable transgene level) was observed up to 60.9 months; the median Tlast was 8.6 months (range: 0.6–60.9 months). The long-term follow-up analysis demonstrates a favorable safety profile of tisagenlecleucel. More than 1 year after tisagenlecleucel infusion, blood and lymphatic system disorders were reported in 11 (13.1%) pts (neutropenia [6.0%], anemia [4.8%], and thrombocytopenia [3.6%]), infection and infestations reported in 34 (40.5%) pts (COVID-19 [17.9%] and pneumonia [11.9%]). Adverse events reported >4 year after tisagenlecleucel infusion will be presented at congress. Second primary malignancies (defined as any new cancer occurring post infusion regardless of tisagenlecleucel relationship) were reported in 7 (7.2%) pts, including 2 events each of basal cell carcinoma, myelodysplastic syndrome, squamous cell carcinoma of skin, and 1 event each of acute myeloid leukemia, bladder transitional cell carcinoma, Bowen's disease, malignant melanoma, and metastatic squamous cell carcinoma. In total, 22 pts died during the study, causes of death includes disease progression (n=8), AEs (n=13, majorly infections), and euthanasia.

Conclusions:After a median follow-up of >5 years, tisagenlecleucel continues to demonstrate durable responses and prolonged survival in pts with r/r FL including in pts with high-risk disease characteristics. No new safety signals were reported. More than 75% of patients were alive, and approximately half remained progression-free at this final analysis, indicating the curative potential of tisagenlecleucel in r/r FL.

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2025
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