Background
Seamless-design phase I TRANSCEND NHL 001 enrolled 344 patients with relapsed/refractory large B-cell lymphoma to receive lisocabtagene maraleucel (liso-cel, a CD19-directed CAR-T given as sequential CD8+ and CD4+ components) 2-7 days after fludarabine (30 mg/m2) + cyclophosphamide (300 mg/m2) conditioning x3 days.
Interventions and follow up
Regimen: Liso-cel single infusion at one of three dose levels (FDA label 50-110 x 10^6 CAR-T cells) after Flu/Cy lymphodepletion in adults with R/R LBCL.
Eligibility: ≥18 yr, PET-positive R/R LBCL after ≥2 lines (incl. rituximab + anthracycline); prior auto/allo-HCT, moderate renal impairment, EF 40-50%, low ALC, and secondary CNS disease permitted. Bridging therapy allowed.
Primary endpoint: ORR and safety.
mFollow up: 12 months.
Eligibility: ≥18 yr, PET-positive R/R LBCL after ≥2 lines (incl. rituximab + anthracycline); prior auto/allo-HCT, moderate renal impairment, EF 40-50%, low ALC, and secondary CNS disease permitted. Bridging therapy allowed.
Primary endpoint: ORR and safety.
mFollow up: 12 months.
Results
Population: median age 63, ECOG 0-1 99%; 51% DLBCL NOS, 29% transformed indolent, 13% DHL/THL, 6% PMBCL, 1% G3B FL; 67% refractory, 33% prior auto-HCT, 3% allo-HCT, 3% secondary CNS; 59% bridging; 51% had ≥3 prior lines.
ORR (efficacy-evaluable): 73% (CR 53%).
ORR (overall): 61% (CR 44%).
Median DoR: not reached (8.6 to NR).
mPFS: 6.8 months (3.3-14.1); 6-mo PFS 51.4%, 12-mo PFS 44.1%.
mOS: 21.1 months (13.3-NR); 6-mo OS 74.7%, 12-mo OS 57.9%.
Dose levels: no difference in outcomes across the three dose levels.
ORR (efficacy-evaluable): 73% (CR 53%).
ORR (overall): 61% (CR 44%).
Median DoR: not reached (8.6 to NR).
mPFS: 6.8 months (3.3-14.1); 6-mo PFS 51.4%, 12-mo PFS 44.1%.
mOS: 21.1 months (13.3-NR); 6-mo OS 74.7%, 12-mo OS 57.9%.
Dose levels: no difference in outcomes across the three dose levels.
Adverse events
CRS (Lee/CTCAE): 42% any grade, 2% grade ≥3; median onset 5 days, median resolution 5 days.
ICANS (CTCAE): 30% any grade, 10% grade ≥3; median onset 9 days, median resolution 11 days.
Hematologic/infections: grade ≥3 cytopenias (neutropenia, anemia, thrombocytopenia) were the most common toxicities; infections occurred and were managed supportively.
ICANS (CTCAE): 30% any grade, 10% grade ≥3; median onset 9 days, median resolution 11 days.
Hematologic/infections: grade ≥3 cytopenias (neutropenia, anemia, thrombocytopenia) were the most common toxicities; infections occurred and were managed supportively.
Conclusions
Liso-cel produces high, durable responses in R/R LBCL (ORR 73%, CR 53%) with a comparatively low rate of grade ≥3 CRS (2%), supporting its activity in a broad, including higher-comorbidity, population.
Key Limitations
Single-arm design with a difference between efficacy-evaluable and overall-cohort response rates due to manufacturing/logistics attrition. Cross-trial comparisons of CRS/ICANS rates with axi-cel and tisa-cel are confounded by differing grading scales and patient selection.
Clinical Context
TRANSCEND supported FDA approval (2021) of liso-cel for R/R LBCL after ≥2 prior lines, one of three CD19 CAR-T options endorsed by ASCO/ESMO guidance. TRANSFORM later established liso-cel in the second-line setting for primary-refractory or early-relapse disease.