The Lancet. Oncology
Zamtocabtagene autoleucel, a tandem CD20-CD19-directed CAR T-cell therapy, for second line treatment of large B-cell lymphoma in patients ineligible for transplantation (DALY 2-EU): primary analysis of an open-label, multicentre, randomised phase 2 study
By Borchmann P, van Meerten T, Iacoboni G and 22 others.
Abstract
Background
Anti-CD19 CAR T-cell therapy is the standard second-line treatment for patients with relapsed or refractory large B-cell lymphoma. However, there is no evidence from randomised controlled trials in patients ineligible for transplantation. To address this gap, we compared zamtocabtagene autoleucel (zamto-cel), a CAR T-cell therapy directed at CD20 and CD19, with rituximab-gemcitabine-oxaliplatin (R-GemOx) chemoimmunotherapy in patients ineligible for transplantation with relapsed or refractory large B-cell lymphoma.
Methods
DALY 2-EU is an open-label, multicentre, randomised, phase 2 trial conducted at 45 centres across 12 countries in Europe. Eligible patients were adults (aged ≥18 years) with second-line relapsed or refractory large B-cell lymphoma confirmed histologically who were ineligible for transplantation and had received first-line chemoimmunotherapy containing a combination of an anthracycline-based regimen and an anti-CD20 monoclonal antibody, with Eastern Cooperative Oncology Group performance status score of 2 or less. Patients were randomly assigned (1:1) to zamto-cel (single intravenous infusion of 2·5 × 106 fresh (ie, non-cryopreserved) CAR T-cells per kg, capped at 100 kg, produced in a closed automated system) or R-GemOx (rituximab [375 mg/m2 intravenously on day 1], gemcitabine [1000 mg/m2 intravenously on day 1 or 2], and oxaliplatin [100 mg/m2 intravenously on day 1 or 2] administered for up to eight 14-day cycles). Randomisation was done with an interactive web response system and stratified by age, gender, lactate dehydrogenase, International Prognostic Index, histology, time to relapse after the start of first-line therapy, and country. The primary endpoint was event-free survival assessed by a masked independent review committee and compared all patients randomly assigned to the zamto-cel and R-GemOx groups using a one-sided log-rank test. Safety was assessed in all patients who received study treatment. This ongoing trial is registered with ClinicalTrials.gov (NCT04844866).