Background
Phase 2 open-label single-arm study. 74 patients with R/R mantle cell lymphoma after ≥1 prior line including a BTK inhibitor. Brexucabtagene autoleucel (KTE-X19) is a CD19-targeted CAR-T using a CD28 co-stimulatory domain with B-cell depletion during leukapheresis to accommodate high circulating tumor burden in MCL.
Interventions and follow up
Regimen: Leukapheresis → conditioning (fludarabine 30 mg/m² × 3d + cyclophosphamide 500 mg/m² × 3d) → single infusion of brexucabtagene autoleucel 2×10⁶ CAR-T cells/kg
Bridging therapy: Permitted (BTKi or steroids)
Primary endpoint: ORR by independent review committee
Median follow up: 12.3 months (primary); long-term follow-up ongoing
Bridging therapy: Permitted (BTKi or steroids)
Primary endpoint: ORR by independent review committee
Median follow up: 12.3 months (primary); long-term follow-up ongoing
Results
ORR (primary): 93% (95% CI 84–98%)
CR rate: 67%
12-mo DOR (responders): 83%
12-mo PFS: 61%
12-mo OS: 83%
mPFS (long-term): 29 months
CR rate: 67%
12-mo DOR (responders): 83%
12-mo PFS: 61%
12-mo OS: 83%
mPFS (long-term): 29 months
Adverse events
CRS: Any grade 91% (grade ≥3: 15%); median onset 2 days
ICANS: Any grade 63% (grade ≥3: 31%) — higher than DLBCL CAR-T; median onset 7 days
Hematologic (grade ≥3): Neutropenia 94%, thrombocytopenia 47%, anemia 40%
Deaths: Two treatment-related (CRS + cardiac arrest; HLH)
ICANS: Any grade 63% (grade ≥3: 31%) — higher than DLBCL CAR-T; median onset 7 days
Hematologic (grade ≥3): Neutropenia 94%, thrombocytopenia 47%, anemia 40%
Deaths: Two treatment-related (CRS + cardiac arrest; HLH)
Conclusions
Brexucabtagene autoleucel achieved 93% ORR with 67% CR in heavily pretreated post-BTKi R/R MCL, establishing the first CAR-T approval in MCL. ICANS rates are higher than in DLBCL, requiring specialized management.
Key Limitations
Single-arm phase 2 without randomized comparator; grade ≥3 ICANS 31% notably higher than DLBCL CAR-T; two treatment-related deaths; bridging therapy required in 75%; access limited by manufacturing time (~4 weeks) and cost; small sample (n=74) limits subgroup precision.
Clinical Context
FDA approved brexucabtagene autoleucel (Tecartus) July 2020 for R/R MCL after ≥1 BTKi — the first CAR-T for MCL; EMA approved December 2020. ESMO recognizes brexu-cel as a standard option for R/R MCL post-BTKi. TRIANGLE established ibrutinib + ASCT as a frontline option; brexu-cel is reserved for R/R post-BTKi disease.