TRANSCEND FL: Phase 2 Study Results of Lisocabtagene Maraleucel in Patients With R/R Follicular Lymphoma

Introduction

• Patients with R/R indolent NHL (iNHL), particularly those with high-risk features, have poor outcomes.
• TRANSCEND FL (NCT04245839), a global, phase 2, single-arm, multicohort, pivotal study assessed efficacy and safety of the anti-CD19 CAR T cell therapy liso-cel in pts with R/R iNHL.
• We report primary analysis results in pts with R/R FL, with safety in all liso-cel–treated pts (i.e., second-line or later [2L+] pts; safety set) and efficacy focused on pts in third line or later (3L+).

Methods

• Eligible patients with R/R FL included 3L+ pts and second-line (2L) pts with disease progression within 24 mo (POD24) of diagnosis and/or modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
• All patients received ≥1 prior combination systemic therapy, including an anti-CD20 antibody and an alkylator.
• Patients received liso-cel (100 × 106 CAR+ T cells) after lymphodepleting chemotherapy. Bridging therapy was allowed.
• The primary endpoint was ORR per independent review committee (IRC) by PET/CT using Lugano 2014 criteria.
• Secondary endpoints included CR rate, duration of response (DOR), PFS, OS, safety, and PK.
• Pharmacodynamics (PD) were exploratory.

Results

• At data cutoff (January 27, 2023), of 139 leukapheresed patients, 130 (94%) received liso-cel, 5 received nonconforming product, and 124 (89%) were efficacy evaluable (EE) per IRC.
• In patients with 3L+ FL, median (range) age was 62 y (23–80), 89% had Ann Arbor stage III/IV disease, and 57% were high-risk per FL International Prognostic Index.
• Forty-three percent of patients had POD24, 53% met GELF criteria, and 64% were double refractory to anti-CD20 antibody and an alkylator.
• Median (range) prior lines of therapy was 3 (2–10). Median (range) follow-up was 18.9 mo (0.3–28.2).
• In EE pts with 3L+ FL (n = 101), the primary endpoint of ORR was met at 97.0% (95% CI, 91.6–99.4; one-sided P < 0.0001; Table).
• CR rate was 94.1% (95% CI, 87.5–97.8; one-sided P < 0.0001).
• With a median follow-up of 16.6 mo and 17.5 mo, respectively, median DOR and PFS were not reached; 12-mo DOR and PFS were 81.9% and 80.7%, respectively.
• ORR, CR rate, DOR, and PFS were similar in EE pts with 2L+ FL.
• In the safety set (2L+ FL, n = 130), the most common grade (gr) ≥3 treatment-emergent adverse events (TEAE) were cytopenias; neutropenia was most frequent (65%). One TEAE death due to gr 5 macrophage activation syndrome occurred.
• Cytokine release syndrome (CRS) occurred in 58% of pts (gr 3, 1%; no gr 4–5) and neurological events (NE) in 15% (gr 3, 2%; no gr 4–5).
• Prolonged cytopenia (gr ≥3 laboratory values at Day 29) occurred in 22% of pts and gr ≥3 infection in 5%.

Conclusions

• In patients with R/R FL, liso-cel demonstrated clinically meaningful benefit, with high response rates that were durable, and a favorable safety profile, with low rates of gr ≥3 TEAEs of CRS/NEs, prolonged cytopenia, and infection.

Morschhauser F, Dahiya S, Palomba ML et al. TRANSCEND FL: Phase 2 Study Results of Lisocabtagene Maraleucel (Liso-Cel) in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma (FL). Abstract presented at: ICML 2023, June 13-17, 2023.