Tisagenlecleucel (CD19 CAR-T) delivers 64% 5-year DFS in frontline MRD+ high-risk pediatric/AYA B-ALL

Tisagenlecleucel (tisa-cel) is an autologous CD19-directed CAR-T therapy tested in the global COG AALL1721/CASSIOPEIA Phase 2 trial (NCT03876769) for very high-risk NCI high-risk B-ALL with persistent MRD ≥0.01% by flow cytometry at end of consolidation (n=121 infused; age 1–25). As of August 20, 2025 (median follow-up 38 months), 4-year OS was 85% and DFS without censoring for subsequent anticancer therapy/SCT was 71% at 3 years and 64% at 5 years, with MRD negativity 95% at day 29 and 86% at 3 months—substantially above the historical ~39% 5-year DFS reported for this MRD-defined subgroup on COG AALL0232. Severe immune toxicity was uncommon (CRS 37% with grade ≥3 2%; ICANS 3% with grade ≥3 1%), but nearly half of patients received subsequent anticancer therapy/SCT without prior relapse (48%), complicating attribution of “durability” to CAR-T alone.