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.
Peter Borchmann, Tom van Meerten, Gloria Iacoboni et al.
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In 30 seconds
DALY 2-EU was an open-label, multicentre, randomised phase 2 trial comparing tandem CD20-CD19-directed zamtocabtagene autoleucel (zamto-cel) with R-GemOx in adults with second-line relapsed or refractory large B-cell lymphoma who were ineligible for transplantation. Among 160 randomly assigned patients, median age 74 years, median follow-up was 17.0 months. Event-free survival was longer with zamto-cel: 6·21 months (95% CI 3·84-13·77) versus 2·53 months (1·97-3·35); HR 0·39 (95% CI 0·27-0·58); p<0·0001. Grade 3 or higher treatment-emergent adverse events occurred in 83% and 86%, respectively.
Key findings
- Median event-free survival was 6·21 months with zamto-cel versus 2·53 months with R-GemOx; HR 0·39 (95% CI 0·27-0·58); p<0·0001.
- Grade 3 or higher treatment-emergent adverse events occurred in 63 (83%) of 76 zamto-cel recipients and 65 (86%) of 76 R-GemOx recipients.
- Serious adverse events occurred in 31 (41%) patients receiving zamto-cel and 50 (66%) receiving R-GemOx; CRS and neurotoxicity were reported with zamto-cel.
Why it matters
Randomised evidence in transplant-ineligible patients with relapsed or refractory large B-cell lymphoma has been lacking. This trial found longer event-free survival with zamto-cel than with R-GemOx, while showing substantial severe adverse-event rates in both groups and distinct immune-mediated toxicities with CAR T-cell therapy. These results help inform assessment of second-line options in this population.
What to keep in mind
The study was open-label and phase 2, and follow-up was a median of 17·0 months; the trial is ongoing.