Liso-cel (CD19 CAR-T) Drives 89% ctDNA-MRD Negativity in 3L+ R/R Follicular Lymphoma, Tracking with 36-mo PFS

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed CAR-T cell therapy; in this exploratory TRANSCEND FL (NCT04245839) analysis of third-line or later (3L+) relapsed/refractory follicular lymphoma, ctDNA-based MRD was assessed using PhasED-Seq in 80 patients with evaluable post-infusion ctDNA and efficacy data. MRD negativity was achieved in 89% (71/80) overall and 93% (71/76) among best-responders with CR, with increasing clearance over time (MRD− 68% at month 1, 83% at month 3, 97% at month 24 among ongoing responders); patients with PR/SD/PD (n=4) never became MRD−. Post-infusion MRD− correlated with longer PFS vs MRD+ (P<0.001), especially at month 3 (HR 7.0 [95% CI 3.0–16.2]) with 36-month PFS 80% (MRD−; n=63) vs 38% (MRD+; n=13); even within PET-CR, MRD added separation (36-month PFS 81% for PET-CR/MRD− vs 56% for PET-CR/MRD+, HR 5.0 [95% CI 1.8–13.4]). As clinical context, non–cell-therapy 3L+ FL options like PI3K inhibition (e.g., copanlisib) historically deliver ORR ~58–59% with CR ~19–20% and median PFS ~11–12 months—far below the long-tail PFS implied here, though cross-trial comparisons are inherently noisy.