Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study

Blood. 2023 Apr 6;141(14):1675-1684. doi: 10.1182/blood.2022018730.

Abstract

This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 1:1 ratio to liso-cel (100 × 106 chimeric antigen receptor-positive T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS). In this primary analysis with a 17.5-month median follow-up, median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel compared with SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03575351.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD19 / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Proportional Hazards Models
  • Transplantation, Autologous

Substances

  • Antigens, CD19

Associated data

  • ClinicalTrials.gov/NCT03575351