Résumé
TRANSCEND FL primary analysis (NCT04245839) demonstrated high response rates and consistent safety profile as previously reported with liso-cel in 2L+ FL, including high-risk 2L FL. Here, we report outcomes by BT status and safety in outpatients.
Consented patients with 2L+ FL received liso-cel; patients with 2L FL had progression of disease ≤24 months from diagnosis after treatment with anti-CD20+alkylator ≤6 months of FL diagnosis and/or met mGELF criteria. Optional BT per investigator was allowed during liso-cel manufacturing with reconfirmation of PET/CT-positive FL before liso-cel infusion. Primary endpoint was ORR per independent review committee; secondary endpoints included CR rate, duration of response (DOR), PFS, OS, and safety. Comparisons between BT and non-BT subgroups are descriptive. Outpatient monitoring occurred per investigator's discretion. Participating study sites had a multidisciplinary CAR T-cell therapy team and SOPs for cytokine release syndrome (CRS)/neurological event (NE) management.
Of 139 patients having leukapheresis (BT/non-BT, n=54/85), 130 received liso-cel (BT/non-BT, n=49/81) and 124 were efficacy evaluable (BT/non-BT, n=45/79). Fifteen patients were monitored as outpatients. BT subgroup had higher baseline (screening and pre-lymphodepletion) disease burden versus non-BT. ORR/CR rates were high and similar across subgroups (BT, 93%/93%; non-BT, 99%/95%), with all responders in the BT subgroup achieving CR. With 18.9-month median follow-up, 12-month DOR/PFS/OS rates were high (BT, 88%/82%/87%; non-BT, 81%/83%/96%); medians were not reached. Grade ≥3 laboratory-based cytopenia for BT/non-BT at Day 29 was 37%/14%; most recovered to grade ≤2 by Day 90. Grade 3 CRS/NEs/infections were low across subgroups (BT, 0%/6%/2%; non-BT, 1%/0%/7%), with no grade 4/5 events. Of 15 outpatients, 6/2 experienced CRS/NEs (grade 1/2 events only). Seven outpatients were hospitalized; median (range) time to initial hospitalization was 7 days (4-16) and duration was 5 days (3-8) (no ICU stays).
Liso-cel showed similar efficacy and safety (low rates of severe CRS/NEs/infections) in both subgroups, suggesting BT may slow disease progression (despite higher baseline disease burden), potentially improving outcomes in this high-risk population. Safety in the outpatient setting was consistent with the overall population and with liso-cel in OUTREACH (NCT03744676; LBCL outpatient setting), with no new safety signals.