Background
Phase II JULIET enrolled 165 patients with relapsed/refractory DLBCL to receive tisagenlecleucel (tisa-cel) on day 0 after lymphodepletion with fludarabine (25 mg/m2) + cyclophosphamide (250 mg/m2) x3 days or bendamustine (90 mg/m2) x2 days. Bridging therapy was permitted after leukapheresis.
Interventions and follow up
Regimen: Tisa-cel single infusion (target 5.0 x 10^8 CAR+ viable T cells) after lymphodepletion in adults with R/R DLBCL.
Eligibility: ≥2 prior lines (incl. rituximab + anthracycline); relapse after or ineligible for auto-HCT. Prior CD19 therapy, PMBCL, allo-HCT, and active CNS disease excluded.
Primary endpoint: Best overall response rate (ORR).
mFollow up: 14 months.
Eligibility: ≥2 prior lines (incl. rituximab + anthracycline); relapse after or ineligible for auto-HCT. Prior CD19 therapy, PMBCL, allo-HCT, and active CNS disease excluded.
Primary endpoint: Best overall response rate (ORR).
mFollow up: 14 months.
Results
Population: median age 56, ECOG 0-1 100%, 79% DLBCL/19% transformed FL, 76% stage III/IV; 52% had ≥3 prior lines; 92% received bridging.
Enrollment-to-infusion: of 165 enrolled, 7% manufacturing failure, 30% progressed before infusion; 111 (67%) infused.
ORR (efficacy cohort): 52% (CR 40%).
ORR (overall/ITT): 34%.
Median DoR: not reached.
mPFS (efficacy cohort): not reached (83% at 12 mo among responders).
mOS (efficacy cohort): 12 months (95% CI 7 to NR); overall cohort 8.3 mo (95% CI 5.8-11.7).
12-mo OS: 49% (efficacy) / 40% (overall); 90% among CR patients.
Enrollment-to-infusion: of 165 enrolled, 7% manufacturing failure, 30% progressed before infusion; 111 (67%) infused.
ORR (efficacy cohort): 52% (CR 40%).
ORR (overall/ITT): 34%.
Median DoR: not reached.
mPFS (efficacy cohort): not reached (83% at 12 mo among responders).
mOS (efficacy cohort): 12 months (95% CI 7 to NR); overall cohort 8.3 mo (95% CI 5.8-11.7).
12-mo OS: 49% (efficacy) / 40% (overall); 90% among CR patients.
Adverse events
CRS (Penn/CTCAE): 58% any grade, 22% grade ≥3; median onset 3 days, median duration 7 days.
Neurotoxicity (CTCAE): 21% any grade, 12% grade ≥3; median onset 6 days, median duration 14 days.
Hematologic/infections: prolonged cytopenias and infections occurred; tocilizumab was used for high-grade CRS.
Neurotoxicity (CTCAE): 21% any grade, 12% grade ≥3; median onset 6 days, median duration 14 days.
Hematologic/infections: prolonged cytopenias and infections occurred; tocilizumab was used for high-grade CRS.
Conclusions
Tisa-cel yields durable responses (efficacy-cohort ORR 52%, CR 40%) in heavily pretreated R/R LBCL, with high 12-month OS among CR patients and a manageable but notable CRS/neurotoxicity profile.
Key Limitations
Single-arm phase II with substantial attrition between enrollment and infusion (manufacturing failure and pre-infusion progression), so the ITT ORR (34%) is lower than the efficacy-cohort estimate. The median time from leukapheresis to infusion (54 days) may disadvantage rapidly progressing patients.
Clinical Context
JULIET supported FDA approval (2018) of tisa-cel for R/R LBCL after ≥2 prior lines, one of the CD19 CAR-T options endorsed by ASCO/ESMO guidance alongside axi-cel and liso-cel for third-line therapy.