Impact of bridging therapy (BT) on lisocabtagene maraleucel (liso-cel) treatment in patients (pt) with R/R follicular lymphoma (FL).
Authors: Juan Luis Reguera, Alejandro Martin Garcia-Sancho, John Kuruvilla, Koji Izutsu, Anna Maria Barbui, Borchmann Peter, Stephan Mielke, Maria Lia Palomba, Guillaume Cartron, Hervé Ghesquieres, Hideki Goto, Indumathy Varadarajan, Thalia Farazi, Grace Shih Hui Kao, Min Vedal, Rina Nishii, Jessica Papuga, Franck Morschhauser
Journal: Journal of Clinical Oncology (2024)

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]