EHA 2026 | What are the key findings from the DALY 2-EU trial of zamto-cel in R/R LBCL?

During the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE, the Lymphoma Hub was pleased to speak with Gloria Iacoboni, Vall d'Hebron University Hospital, Barcelona, ES. We asked, What are the key findings from the DALY 2-EU trial of zamtocabtagene autoleucel (zamto-cel) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL)? 

Key points 

• Efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapies has been demonstrated for transplant-eligible patients with R/R LBCL;¹ however, the level of evidence for CAR T-cell therapies in patients who are transplant ineligible should be strengthened. 
• The phase II DALY 2-EU trial (NCT04844866) compared zamto-cel, an autologous non-cryopreserved, tandem CD20-CD19-directed CAR T-cell therapy with a fixed 12-day manufacturing window and an average vein-to-vein time of 14 days, vs standard of care (rituximab + gemcitabine + oxaliplatin [R-GemOx] or polatuzumab vedotin + bendamustine + rituximab [Pola-BR]) in patients with R/R LBCL who are ineligible for transplant.¹ 
• Primary results from the DALY 2-EU trial were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US: 
  • After a median follow-up of 17 months, zamto-cel improved event-free survival (EFS) vs R-GemOx (median EFS, 6.21 months vs 2.53 months; hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.27–0.58; p <0.0001).¹ 
  • The safety profile of zamto-cel was manageable, with low rates of Grade ≥3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS; 1.3%), and cytokine release syndrome (CRS; 5.3%).¹ 
• A protocol amendment in February 2023 allowed one-side crossover from the standard of care arm to zamto-cel as a third-line (3L) therapy for patients who relapsed/progressed ≤1 year after randomization or did not have a partial response in ≥8 weeks or complete response (CR) at end of treatment.² 
• Results from an analysis of patients who crossed over to zamto-cel (n = 29) were presented during the EHA 2026 Congress, June 11–14, 2026, Stockholm, SE: 
  • Neutropenia (55.2%) was the most common hematologic treatment-emergent adverse event (TEAE).² 
  • TEAEs leading to death were reported in four patients (lymphoma progression, n = 2; bronchitis, n = 1; septic shock, n = 1).² 
  • Any-grade CRS and ICANS were reported in 48.3% (Grade 1, 27.6%; Grade 2, 13.8%; Grade 4, 6.9%) and 17.2% (Grade 1, 6.9%; Grade 2, 6.9%; Grade 4, 3.4%) of patients, respectively.² 
  • The best overall response rate was 79.3%, with a CR rate of 65.5%.² 
• In the 3L setting, most intended patients received zamto-cel, and in this mainly refractory population, zamto-cel resulted in clinically meaningful response rates with low rates of severe CRS and ICANS, consistent with second-line treatment.² 

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