Introduction: In the primary analysis of TRANSCEND FL (NCT04245839), an open-label, pivotal study, liso-cel showed high response rates and favorable safety in patients with R/R FL. Here, we report 3-year follow-up (FU) results in patients with 3L+ FL, including efficacy, ety, and longitudinal safety analyses for key AEs.

Methods: Patients were eligible if they had R/R FL after ≥2 prior lines of combination systemic therapy, including an anti-CD20 antibody and an alkylator. Patients received liso-cel after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed with reconfirmation of PET-positive disease before LDC. The primary endpoint was ORR per independent review committee by PET/CT using Lugano 2014 criteria. Secondary endpoints included CR rate, duration of response (DOR), PFS, OS, and safety. Additional post hoc analyses included time to next treatment (TTNT) and efficacy by progression within 24 months (mo) from first-line chemoimmunotherapy (POD24) status (yes vs no) and by prior bendamustine exposure before leukapheresis (yes vs no). Incidences of infections, second primary malignancies (SPM), hypogammaglobulinemia, and grade ≥3 cytopenia (overall and by lineage) were assessed over time from Days (D) 1-30, at 3-mo intervals until Mo 12, at 6-mo intervals until Mo 36, and from Mo 36 until end of study (EOS). Incidences were calculated as the number of patients with ≥1 event divided by the number of patients ongoing during that time period; patients who received a subsequent therapy were excluded from the analysis at the time of initiation of subsequent therapy.

Results: At data cutoff (31 March 2025), 107 patients with 3L+ FL received liso-cel and were evaluable for safety; 103 were efficacy evaluable. Median (range) age was 62 years (23–80); 95 (89%) had Ann Arbor stage III/IV disease; and 61 (57%) were high risk per FLIPI. Fifty-nine patients (55%) had POD24; 69 (64%) were double refractory to anti-CD20 antibody and an alkylator; and 65 (61%) had prior bendamustine exposure.

Median (range) on-study FU was 41.5 mo (0.3–54.0). ORR and CR rate (95% CI) were 97% (92–99) and 94% (88–98), respectively. Medians continued to be not reached for all time-to-event outcomes; 36-mo (95% CI) rates for DOR, PFS, OS, and TTNT were 70% (60–78), 68% (58–76), 86% (78–92), and 75% (66–83), respectively.

Response rates were high regardless of POD24 status: ORR, 96% and 98%; CR rate, 95% and 93%, respectively, for POD24 and non-POD24 patients. At 36 mo, rates for POD24 and non-POD24 patients were: 60% and 82% for DOR, 58% and 80% for PFS, 82% and 91% for OS, and 68% and 85% for TTNT, respectively.

Response rates were high in patients with and without prior bendamustine exposure (ORR, 97% and 98%; CR rate, 93% and 95%, respectively). At 36 mo, rates were similar for patients with and without prior bendamustine exposure: 70% and 69% for DOR, 68% and 67.5% for PFS, 81% and 93% for OS, and 73% and 78.5% for TTNT, respectively.

Treatment-emergent adverse event rates were consistent with the primary and 2-year FU analyses. Grade 3 cytokine release syndrome was reported in 1% (no grade 4/5), grade 3 neurological events in 2% (no grade 4/5). SPMs were reported in 11 patients (10%; 4 additional patients since the 2-year FU analysis; no secondary T-cell malignancies). Grade ≥3 infections were reported in 13 patients (12%), including 7 (7%) in the treatment-emergent (TE) period (≤90 d after infusion) and 8 (7%) in the post-TE period (3 more patients since the 2-year analysis).

AE incidences during the following time periods, D1-30 (n=107); Mo 9-12 (n=94); Mo 18-24 (n=89); Mo 30-36 (n=74) and Mo 36-EOS (n=70), were: 80%, 10%, 6%, 4%, and 4% for grade ≥3 neutropenia; 64%, 43%, 44%, 20%, and 34% for hypogammaglobulinemia; and 4%, 1%, 1%, 4%, and 1% for grade ≥3 infections. Longitudinal data on additional AEs and time periods will be presented.

Conclusions: In patients with 3L+ FL, a single infusion of liso-cel demonstrated remarkable efficacy, with durable responses and high 3-year survival rates, regardless of POD24 status or prior bendamustine exposure. No new safety signals were identified. Grade ≥3 neutropenia and hypogammaglobulinemia decreased over time and severe infections remained low, further underscoring the favorable long-term safety profile of liso-cel in patients with 3L+ FL.

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2025
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