Miltenyi Biomedicine has announced significant findings from the pivotal DALY 2-EU trial, which assesses the efficacy and safety of zamtocabtagene autoleucel (zamto-cel) in treating patients with second-line relapsed or refractory large B-cell lymphoma (r/r LBCL). The results, revealed on December 7, 2025, demonstrate zamto-cel’s superiority over standard chemotherapy regimens in patients unable to undergo stem cell transplants due to various medical factors.
The study, which involved a population characterized by older age and high-risk disease features, showed that zamto-cel significantly improved event-free survival compared to the chemoimmunotherapy regimens of R-GemOx or Pola-BR. The median age of participants was 74 years, with 57% of patients classified as having a high International Prognostic Index (IPI≥ 3) and 67% presenting with advanced-stage disease.
Positive Outcomes for High-Risk Patients
Dr. Peter Borchmann, the lead investigator of the DALY 2-EU trial and Assistant Medical Director at the University Hospital of Cologne, emphasized the importance of these findings. “Zamto-cel demonstrated clinically meaningful and statistically significant superiority over R-GemOx in transplant-ineligible patients with high-risk disease, improving event-free survival while maintaining a favorable tolerability profile,” he stated. His remarks highlight the potential of zamto-cel as an innovative treatment option for patients with limited choices.
According to Miltenyi Biomedicine’s Chief Executive Officer Dr. Toon Overstijns, the results of the DALY 2-EU trial represent a significant milestone in their commitment to advancing cell and gene therapies. He noted that zamto-cel, being the first tandem CD20-CD19 directed, non-cryopreserved CAR-T cell therapy, presents a substantial clinical benefit, enhancing treatment options for patients facing high-risk lymphomas.
Trial Details and Future Implications
The DALY 2-EU trial, registered under NCT04844866, is a randomized, multi-center, open-label Phase II study conducted across 12 countries in the European Union. It compares the genetically engineered autologous T-cells expressing anti-CD20 and anti-CD19 specific chimeric antigen receptor zamto-cel against standard chemotherapy treatments. Participants, aged 18 years and older with r/r LBCL, had to be refractory or relapsed within 24 months of initial treatment and ineligible for stem cell transplants.
In the trial, patients were randomly assigned to receive either zamto-cel (n=82) or the comparator chemotherapy regimens (n=86). The primary endpoint of the trial was event-free survival, assessed by a blinded independent review committee, defined as the duration from randomization to disease progression or the need for new anti-lymphoma therapy. Secondary endpoints included progression-free survival, best complete response rate, duration of complete response, and overall survival.
At the data cutoff, the trial allowed for crossover; 29 patients received zamto-cel after failing to respond to R-GemOx or Pola-BR. The results demonstrated that zamto-cel was well tolerated among the primarily elderly and high-risk patient population, suggesting a promising safety profile.
Miltenyi Biomedicine’s commitment to advancing innovative cancer treatments is evident in their ongoing research with zamto-cel. This investigational CAR-T therapy is designed to target both CD20 and CD19, and is being studied for various B-cell malignancies, including other forms of lymphoma and neoplasms.
The findings of the DALY 2-EU trial will be further analyzed with extended follow-up periods, with additional data expected to be presented at future medical meetings. As researchers aim to provide enhanced treatment options for vulnerable patient populations, zamto-cel’s efficacy and safety could play a pivotal role in the evolving landscape of therapies for high-risk lymphomas.
