Résumé
7068
Background: TRANSCEND FL primary analysis (NCT04245839) demonstrated very high response rates and manageable safety with liso-cel in second-line or later (2L+) FL, including 2L high-risk FL. Here, we report outcomes in subgroups of pts by BT status. Methods: TRANSCEND FL, a global, phase 2, single-arm, open-label study, evaluated liso-cel in adults with 2L+ R/R FL. Pts with 2L FL had progression of disease ≤ 24 mo (POD24) from diagnosis after treatment with anti-CD20 + alkylator ≤ 6 mo of FL diagnosis and/or met modified Groupe d’Etude des Lymphomes Folliculaires (mGELF) criteria. Pts received liso-cel after lymphodepleting chemotherapy (LDC). Optional BT per investigator was allowed during liso-cel manufacturing; reconfirmation of PET/CT-positive FL was required before LDC/liso-cel infusion to be considered efficacy evaluable (EE). PET/CT-based response assessments were performed at baseline (after end of BT and ≤ 7–14 days before LDC) and at post-infusion day 29 onward up to 60 mos. Primary endpoint was ORR per independent review committee (IRC); secondary endpoints included CR rate, duration of response (DOR), PFS, OS, and safety. Comparisons between BT and no BT (NBT) subgroups are descriptive. Results: Of 139 leukapheresed pts: 54 received BT; 130 were treated with liso-cel and 124 were EE (BT, n = 45; NBT, n = 79). BT pts had higher disease burden at baseline vs NBT: stage III/IV (94% vs 82%), sum of the product of perpendicular diameters ≥ 50 cm
2
before LDC per IRC (26% vs 14%), FL International Prognostic Index score 3–5 (78% vs 38%), met mGELF criteria (72% vs 48%), double refractory to anti-CD20 + alkylator (78% vs 52%), and POD24 from initial immunochemotherapy (65% vs 52%). ORR/CR rates were high and similar across subgroups, with all BT responders achieving CR (Table). Median DOR, PFS, and OS were not reached (NR) in both subgroups (Table), with a median follow-up of 18.9 mo. Grade (gr) ≥ 3 treatment-emergent AEs in BT vs NBT pts were reported in 82% vs 70%, most commonly, neutropenia (69% vs 52%), anemia (18% vs 5%), and thrombocytopenia (18% vs 5%). Gr ≥ 3 lab-based cytopenia was numerically higher in BT vs NBT at Day 29 (37% vs 14%), but most pts recovered to gr ≤ 2 by Day 90. In BT vs NBT pts, any-grade cytokine release syndrome (CRS; 51% vs 62%) and neurological events (NE; 12% vs 17%) were numerically lower, but gr 3 CRS/NEs/infections were similarly low across subgroups (BT, 0/6%/2%; NBT, 1%/0/7%, respectively), with no gr 4 or 5 events. Conclusions: Liso-cel showed equal clinical efficacy and safety (low rates of severe CRS/NEs/infections) in BT vs NBT pts, suggesting BT may mitigate worse outcomes and AEs associated with high tumor burden/high-risk features. Clinical trial information: NCT04245839 . [Table: see text]