Background
Phase II, single-arm study. 61 patients with R/R DLBCL who were not candidates for ASCT (transplant-ineligible) and had received exactly 1 prior line. Tested lisocabtagene maraleucel (liso-cel), a CD19-targeted 4-1BB CAR-T (defined CD4:CD8 ratio), as second-line therapy in this typically poor-prognosis population excluded from the pivotal TRANSFORM trial.
Interventions and follow up
Regimen: Lisocabtagene maraleucel (liso-cel) 100 × 10⁶ CAR-T cells IV single infusion after fludarabine/cyclophosphamide lymphodepletion in transplant-ineligible R/R LBCL (second line)
Bridging therapy: Permitted between leukapheresis and lymphodepletion
Primary endpoint: Overall response rate (independent review committee)
Median follow-up: 12.3 months
Bridging therapy: Permitted between leukapheresis and lymphodepletion
Primary endpoint: Overall response rate (independent review committee)
Median follow-up: 12.3 months
Results
ORR (primary): 80.3% (95% CI 68.0–89.4%)
CR rate: 54.1%
mDOR (responders): 12.1 months
mPFS: 7.0 months
mOS: Not reached (12-month OS 50.5%)
CR rate: 54.1%
mDOR (responders): 12.1 months
mPFS: 7.0 months
mOS: Not reached (12-month OS 50.5%)
Adverse events
CRS/ICANS: CRS any grade 45.9%, grade ≥3 1.6%; ICANS any grade 26.2%, grade ≥3 9.8%
Hematologic: Grade ≥3 neutropenia 60.7%, thrombocytopenia 36.1%, anemia 14.8%
Fatal: One treatment-related death (CRS + sepsis)
Hematologic: Grade ≥3 neutropenia 60.7%, thrombocytopenia 36.1%, anemia 14.8%
Fatal: One treatment-related death (CRS + sepsis)
Conclusions
Liso-cel demonstrated high response rates (80.3% ORR, 54.1% CR) in transplant-ineligible R/R DLBCL patients, a population historically treated with palliative intent. This supported FDA approval of liso-cel in the 2L setting regardless of transplant eligibility.
Key Limitations
Single-arm Phase II with no comparator and modest sample size (n=61) — outcomes cannot be directly contrasted with chemoimmunotherapy. Short median follow-up (12.3 months) limits assessment of response durability. Transplant-ineligible population is heterogeneous (age, comorbidity, prior-line timing), and selection criteria may not generalize. One treatment-related death highlights toxicity risk in a less-fit cohort.
Clinical Context
PILOT supported FDA expansion of liso-cel (Breyanzi) in June 2022 to 2L R/R LBCL in patients not eligible for transplant, complementing the TRANSFORM data in transplant-eligible patients. EMA has approved liso-cel for R/R LBCL. ESMO and ASCO guidance recognize CAR-T as a second-line option in transplant-ineligible R/R LBCL with chemorefractory or early-relapsing disease.