Miltenyi Biomedicine announced significant findings from the pivotal DALY 2-EU trial, demonstrating that zamtocabtagene autoleucel, known as zamto-cel, shows clinically meaningful superiority over traditional chemoimmunotherapy for patients with relapsed or refractory large B-cell lymphoma (r/r LBCL). This development is particularly notable for patients deemed ineligible for stem cell transplants due to age or other health factors.
The trial, which included a high-risk population, reported that zamto-cel was well-tolerated, with a manufacturing time of just 12 days leading to a vein-to-vein time of 14 to 16 days. This efficiency reduces the need for bridging therapy, offering hope for patients facing rapid disease progression.
Key Findings from the DALY 2-EU Trial
Conducted in 12 countries across Europe, the DALY 2-EU trial involved a randomized, open-label study comparing zamto-cel to standard treatments, including R-GemOx and Pola-BR. The results indicated that zamto-cel significantly improved event-free survival (EFS) compared to R-GemOx.
The trial enrolled 168 patients, with a median age of 74 years. Notably, 57% of participants had a high International Prognostic Index (IPI ≥ 3), and 67% presented with advanced-stage disease (III/IV). Data showed a median EFS of 6.2 months for zamto-cel compared to just 2.5 months for R-GemOx, with a hazard ratio of 0.39 (p < 0.0001).
Progression-free survival (PFS) was also significantly longer for zamto-cel, at 8.5 months versus 3.3 months for R-GemOx (hazard ratio 0.43; p < 0.0001). The overall response rate (ORR) was 72% for zamto-cel, with a complete response rate (CRR) of 54%, compared to an ORR of 45% and CRR of 14% for the comparator group.
“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,” stated Dr. Peter Borchmann, Lead Investigator and Assistant Medical Director in the Department of Hematology and Oncology at the University Hospital of Cologne.
Implications for Patients and Future Research
The findings from the DALY 2-EU trial represent a significant milestone in developing cell and gene therapies. According to Dr. Toon Overstijns, Chief Executive Officer of Miltenyi Biomedicine, these results underscore the potential of zamto-cel to provide treatment options for patients with limited choices.
Zamto-cel is noteworthy for being the first tandem CD20-CD19 directed, non-cryopreserved CAR-T cell therapy. Its dual targeting mechanism aims to minimize relapse risks associated with CD19-directed therapies, enhancing the treatment landscape for high-risk patients.
As the trial progresses, additional analyses are planned, with results expected at future medical meetings. The ongoing research into zamto-cel includes trials for other B-cell malignancies, such as mantle cell lymphoma and Richter’s transformation.
Miltenyi Biomedicine’s commitment to innovative cancer treatments highlights the importance of advancing therapeutic options for patients facing challenging diagnoses. With promising results from the DALY 2-EU trial, the company is poised to make a significant impact in the field of oncology.
