Miltenyi Biomedicine has announced significant findings from the pivotal DALY 2-EU trial, which assessed the efficacy and safety of zamtocabtagene autoleucel (zamto-cel) in patients with relapsed or refractory large B-cell lymphoma (r/r LBCL). The trial demonstrated that zamto-cel achieved clinically meaningful superiority over standard chemoimmunotherapy treatments, including R-GemOx and Pola-BR, particularly in a high-risk patient population.
The results were revealed on December 7, 2025, during a press release from the company based in Bergisch Gladbach, Germany. The DALY 2-EU trial included a patient group characterized by older age and significant disease risk factors, with a median age of 74 years. Notably, 57% of participants had a high International Prognostic Index (IPI ≥ 3), and 67% were diagnosed at stage III or IV.
The trial’s findings indicate that zamto-cel was well-tolerated among the predominantly elderly population. According to Dr. Peter Borchmann, the lead investigator and Assistant Medical Director at the Department of Hematology and Oncology at the University Hospital of Cologne, zamto-cel showed remarkable efficacy, improving event-free survival while maintaining a favorable tolerability profile.
Dr. Toon Overstijns, Chief Executive Officer of Miltenyi Biomedicine, emphasized the importance of these results, stating that they signify a milestone in the company’s commitment to advancing cell and gene therapies. Zamto-cel is distinguished as the first tandem CD20-CD19 directed, non-cryopreserved CAR-T cell therapy. Its unique formulation is designed to minimize the risk of relapse, a common issue with existing CD19-directed therapies, by targeting both CD20 and CD19 antigens.
The manufacturing time for zamto-cel is notably efficient at 12 days, resulting in a vein-to-vein time of 14-16 days. This rapid production timeline reduces the reliance on bridging therapy, which is critical for patients requiring urgent treatment.
In the primary analysis of the trial, patients were randomly assigned to receive either zamto-cel (n=82) or R-GemOx/Pola-BR (n=86). Notable efficacy results included a median event-free survival (EFS) of 6.2 months for zamto-cel compared to 2.5 months for R-GemOx, with a hazard ratio of 0.39 (95% CI 0.27-0.58; p<0.0001). Additionally, the median progression-free survival (PFS) was significantly longer at 8.5 months for zamto-cel versus 3.3 months for the standard treatment.
The overall response rate (ORR) was impressive, with zamto-cel achieving 72% and a complete response rate (CRR) of 54%. In contrast, R-GemOx demonstrated an ORR of 45% and a CRR of 14%.
Safety results indicated that zamto-cel was well-tolerated in this high-risk population, with grade ≥ 3 cytokine release syndrome reported in only 4 patients (5.3%) and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) in 1 patient (1.3%).
The DALY 2-EU trial, registered under NCT04844866, is a randomized, multi-center, open-label Phase II study conducted across 12 countries within the European Union. It aims to provide a comprehensive evaluation of zamto-cel against established chemotherapy treatments for patients who are ineligible for a stem cell transplant.
This trial represents a significant advancement in the treatment options available for patients with r/r LBCL, particularly those facing limited therapeutic choices due to age or comorbidities. The positive results are aligned with previous findings from other studies involving zamto-cel, reinforcing its potential as a transformative therapy in the field of hematology.
As Miltenyi Biomedicine continues to explore the capabilities of zamto-cel, further analyses and longer follow-up periods are anticipated, with data to be shared at future medical meetings. The ongoing research reflects a broader commitment to enhancing treatment strategies for patients grappling with challenging hematological conditions.
