^* The results of the DALY 2-EU study show that zamtocabtagene is autoleucel
(Zamto-cel) in patients with relapsed/refractory large B-cell
Lymphoma (r/r LBCL) has a clinically significant superiority over the
chemoimmunotherapy(1)
* Zamto-cel was well tolerated in the majority of patients. The DALY 2-EU
Study included a high-risk population characterized by older age and
clinically unfavorable disease characteristics
* A manufacturing time of 12 days resulted in a vein-to-vein time of
14-16 days and reduced the likelihood of bridging
Therapy was required.
BERGISCH GLADBACH, Germany, Dec. 08, 2025 (GLOBE NEWSWIRE) — Miltenyi
Today Biomedicine has the results of the pivotal DALY 2-EU study
announced. This study evaluated the effectiveness and safety of
Zamtocabtagene Autoleucel (Zamto-cel) compared to standard
Chemoimmunotherapy (R-GemOx or Pola-BR) as second-line therapy in patients
with relapsed or refractory large B-cell lymphoma (r/r LBCL)
assessed based on their age, comorbidities or others
were not eligible for a transplant for medical reasons.
The primary analysis showed that zamto-cel was effective in transplant-ineligible patients
Patients at high risk of rapid disease progression
significant and clinically relevant superiority over the
chemoimmunotherapy (R-GemOx).(1) This study population was characterized by a
Older age and clinically unfavorable disease characteristics: This
median age was 74 years, 57% of patients had a high
International Prognostic Index (IPI >= 3) and 67% were in
Stage III/IV of the disease. Zamto-cel was in this predominantly older
High-risk population well tolerated.(1)
Dr. Peter Borchmann, principal investigator of the DALY 2-EU study and deputy
medical director of the department of hematology and oncology at
Cologne University Hospital, explained: Zamto-cel showed at
Patients with high-risk disease who are unsuitable for transplantation receive clinical treatment
significant and statistically significant superiority over R-GemOx by
it improved event-free survival and at the same time a favorable one
Tolerability profile. These results highlight the potential
of Zamto-cel as an important new treatment option for a clinically vulnerable population
Patient group with limited therapeutic options.”
Dr. Toon Overstijns, Chief Executive Officer of Miltenyi Biomedicine, added
added:?The results of the DALY 2-EU study are an important milestone in
our commitment to the further development of cell and gene therapies. Zamto
cel, the first tandem CD20-CD19-targeted, non-cryopreserved CAR-T
Cell therapy, showed significant clinical benefit with promise
Efficacy and safety. This makes us urgently provide it
needed treatment options for patients with high-risk lymphoma
Step closer.”
* Zamto-cel is the first tandem CD20-CD19 targeted non-cryopreserved one
chimeric antigen receptor T cell therapy (CAR-T). The main mechanisms for a
Recurrence after treatments with CD19-targeted CAR T-cell therapies are the
limited persistence of CAR-T cells, inhibition of their function and the
CD19-specific antigen escape. To reduce the risk of recurrence due to
To minimize CD19 antigen escape, Zamto-cel uses a dual antigen
Targeting CD20 and CD19. Zamto-cel has a manufacturing time of 12
days, resulting in a vein-to-vein time of 14 to 16 days. Through this
The likelihood of bridging therapy is reduced
becomes necessary
Primary results of the DALY 2-EU study(1)
At the data cutoff date, patients were randomized and the
Treatment with Zamto-cel (n = 82) or treatment with R-GemOx/Pola-BR
(n = 86). The study also allowed a crossover: 29 patients
received Zamto-cel after not responding to R-GemOx (n = 28) or not responding to Pola-
BR (n = 1).
Efficacy results (assessed by the blinded independent
Review Board, BIRC)
*Median event-free survival (EFS) for Zamto-cel was 6.2 months
(95% CI 3.8-13.8) compared to 2.5 months (95% CI 2.0-3.3) for R-GemOx
(HR 0.39; 95% CI 0.27-0.58; p = 3 was in four patients
(5.3%) observed.
* Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS).
occurred in one patient (1.3%).
About DALY 2-EU(2)
DALY 2-EU (NCT04844866) is a pivotal, randomized,
multicenter, open-label phase II study in twelve countries within the EU
is carried out. The study will evaluate the safety and effectiveness of
genetically modified autologous T cells that have an anti-CD20 and
CD19-directed chimeric antigen receptor (Zamtocabtagene Autoleucel, Zamto-cel)
express, compared to chemoimmunotherapy (CIT) (rituximab, gemcitabine
andoxaliplatin [R-GemOx]) or polatuzumab vedotin plus bendamustine/rituximab
(Pola-BR) as second-line therapy for primary relapsed/refractory
large B-cell lymphoma (r/r LBCL). According to our knowledge, this is the
only randomized CAR-T study to date in this patient group
was carried out.
Adults with r/r LBCL within 24 months were eligible to participate
were refractory to their first-line treatment or developed a recurrence
had at least one anthracycline- and one rituximab-containing therapy
had received and were not eligible for a stem cell transplant.
Participants were randomized 1:1 to receive either
Zamto-cel or CIT (R-GemOx/Pola-BR). Zamto-cel was designed as an individual, not
cryopreserved infusion at a dose of 2.5 x 10^6 CAR-transduced T-
Cells per kilogram of body weight after lymphodepletion with fludarabine and
Cyclophosphamide administered. The patients included in the comparison arm
were randomized to receive either R-GemOx or Pola-BR.
The primary endpoint of the study is event-free survival (EFS), which is determined by
is assessed by a blinded, independent review committee (BIRC) and
is defined as the time from randomization to objective
Progression of the disease, failure to achieve partial (PR) or
complete response (CR) at or after week 8, leading to initiation of a new one
Anti-lymphoma therapy results in or death from any cause. Secondary endpoints
include progression-free survival (PFS), the best complete response rate
(CRR), duration of complete response (DOR) and overall survival (OS).
These data will be reviewed as part of a pre-planned EFS interim analysis
published with a median follow-up period of 17 months. More
Analyzes with longer follow-up periods are planned and ongoing
presented at future meetings.
The results of the DALY-2-EU study complement previous publications
Zamto-cel in other indications and populations including:
* DALY II USA (NCT04792489), a Phase II, multicenter, open-label, single-arm
Study of Zamto-cel in patients with r/r DLBCL who already have at least
have received two prior lines of therapy, including a monoclonal
Anti-CD20 antibodies and an anthracycline-containing regimen, and
who have a measurable disease according to the Lugano Classification 2014
is present. The ORR in the evaluable patient population (n = 59) was assessed
by an independent radiology panel, was 72.9% (95% CI,
59.7-83.6) with a CRR of 49.2% (95% CI, 35.9-62.5).
* A special cohort was also used in the DALY II USA clinical trial
for r/r lymphomas of the central nervous system. In this cohort of
16 patients had an overall response rate of 80% and 100%, respectively
a complete response rate of 50% and 100% in PCNSL (primary
CNS lymphoma) or SCNSL group (secondary CNS lymphoma).
* Zamto-cel is currently being used in r/r mantle cell lymphoma (MCL) and in r/r
Richter transformation (RT) examined
About Zamtocabtagene Autoleucel (Zamto-cel)
Zamto-cel is an experimental autologous chimera
Antigen receptor (CAR) T cell therapy targeting both CD20 and CD19
aimed. It is being used in clinical trials to treat relapsed or
refractory B-cell malignancies, including large B-cell lymphoma
(LBCL), diffuse large B-cell lymphoma (DLBCL), primary and secondary
Central nervous system (CNS) lymphoma, mantle cell lymphoma (MCL), Richter’s
Transformation (RT) and other B-cell neoplasms.
Zamto-cel is developed using Miltenyi’s proprietary platform, a
closed, automated system. The manufacturing time of
12 days allows for a vein-to-vein time of 14-16 days, making the
Reduced need for bridging therapy and access to cell therapies
for high-risk patients with urgent need for therapy. There none
Cryopreservation is required, cryopreservation-related ones are not required
logistical steps and costs.
About Miltenyi Biomedicine
Miltenyi Biomedicine aims to treat patients with severe
Diseases Access to innovative cancer treatments and regenerative therapies
to provide. The company develops new ones using the latest technologies
Approaches for difficult-to-treat blood cancers and exploits the potential
CAR technology to fundamentally improve patient care.
Miltenyi Biomedicine is currently studying its first cell therapy product.
About Miltenyi Biotec
Miltenyi Biotec is a global leader in technologies and services for
patient-specific cell and gene therapies and sets scientific standards
Transforming discoveries into practical treatments for personalized medicine. With
The company supports biomedical products with over 35 years of experience
discoveries and translates them into clinical applications, enabling patients
Gain access to new therapies. With its integrated solutions including
GMP-certified cell factories, Miltenyi Biotec offers therapy developers over
its global CDMO division Miltenyi Bioindustry received expert advice from the
Process development through to commercialization.
contact
Miltenyi Biomedicine
Jasmine Oberwalleney
Friedrich-Ebert-Strasse 68
51429 Bergisch Gladbach, Germany
[email protected] (mailto:[email protected])
References
1. Borchmann P, et al. Zamtocabtagene-autoleucel, a tandem CD20-CD19 directed
CAR-T cell therapy as second-line treatment for Relapsed/Refractory large B-
cell lymphoma: primary analysis of the randomized pivotal DALY 2-EU study.
Presented at the American Society of Hematology (ASH) Annual Meeting.
Abstract #abs25-738.
2. ClinicalTrials.Gov. Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma
Patients (DALY 2-EU). Available at:
https://clinicaltrials.gov/study/NCT04844866. Accessed September 2025.
MAT-GL-ZA-0003
Creation date: December 2025
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