Varnimcabtagene Autoleucel Demonstrates High MRD-Negative Response Rates in Relapsed or Refractory B-Acute Lymphoblastic Leukemia

Clinical Summary:

• Design/Population: The multicenter, phase 2 CART19-BE-02 trial evaluated varnimcabtagene autoleucel, a CD19-directed, 4-1BB–based CAR T-cell therapy, in 32 adults with relapsed or refractory B-cell acute lymphoblastic leukemia treated across 8 centers in Spain. The primary end point was MRD-negative complete remission by next-generation flow cytometry at day 28.
• Key Outcomes: Varnimcabtagene autoleucel produced high rates of MRD-negative complete remission with durable responses and a favorable safety profile, including low rates of severe cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome.
• Clinical Relevance: These findings support varnimcabtagene autoleucel as a promising CAR T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia and provide the basis for planned European regulatory submission.

Valentín Ortiz-Maldonado, MD, Hospital Clínic, Barcelona, Spain, discusses results from the multicenter phase 2 CART19-BE-02 trial evaluating varnimcabtagene autoleucel in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The study assessed a fractionated dosing strategy designed to improve the safety of CD19-directed CAR T-cell therapy while maintaining efficacy.

The trial demonstrated high rates of MRD-negative complete remission with durable responses and manageable toxicity in a heavily pretreated patient population. These findings support broader clinical development of varnimcabtagene autoleucel and have informed plans for a European Medicines Agency marketing authorization application.

Transcript:

Hello everyone, my name is Valentino Ortiz Maldonado, I am a hematologist at Hospital Clínic of Barcelona, and I’m going to talk a little bit about the multicenter CART19-BE-02 trial, which assesses the safety and efficacy of varnimcabtagene autoleucel. 

Varnimcabtagene autoleucel is a second-generation 4-1BB–based CAR construct which is directed towards CD19. Varnimcabtagene autoleucel has been approved in Spain since 2021 for the treatment of adults older than 25 years with relapsed/refractory B-ALL, and this has been achieved through the hospital exemption authorization. In Spain, we do have access to tisagenlecleucel until 25 years of age and after that we only have access to this homegrown product that has been developed entirely at the Hospital Clínic of Barcelona, which is a public health institution in Spain.

The current CART19-BE-02 trial is a phase 2 trial which evaluates the safety and the efficacy of varnimcabtagene autoleucel in a multicenter setting. We have 8 centers that have been enrolling patients throughout Spain and the key inclusion criteria were basically patients older than 18 years with relapsed/refractory B-ALL who had to have any degree of measurable disease in the bone marrow or in peripheral blood by next-generation flow. 

The primary end point was very stringent—it was complete remission with undetectable MRD by next-generation flow with a sensitivity level of 10⁻⁵ in bone marrow and peripheral blood at day +28– it was a very, very stringent primary end point, which is very different from the traditional morphological response that we see in other trials for B-ALL.

We treated 32 patients, the way that we give CAR T cells is quite different from other CAR T-cell trials, we don’t give all the cells in one go we split the dose into 4 increasing fractions of 0.1, 0.3, 0.6, and 2.0 × 10⁶ CAR T cells/kg. Depending on how the patient reacts to every infusion, if the patient develops toxicity, CRS, or ICANS, we can stop and resume if toxicities have resolved. If the patient develops severe toxicities, we just stop, and that’s the highest dose that the patient will receive. Depending on if the patient does not develop severe toxicities, they can receive up to 3 × 10⁶ CAR T cells/kg.

We treated 32 patients with at least 1 varnimcabtagene autoleucel dose and of these, 23 patients were able to receive all 4 doses. This was a very heavily treated population, median age of 40 years and a median of 2 prior treatment lines, including at least 2/3 with prior allogeneic stem cell transplantation.

The important thing is we had a pretty manageable safety profile, with severe CRS incidence of around 12% and also any-grade incidence of ICANS of only 3% of patients. For efficacy, 84% were able to achieve MRD-negative complete response at day 28, which increased up to 95% within the first 3 months in patients receiving the maximum dose, or the full 3 × 10⁶ CAR T cells/kg. For durability, we have quite durable responses, with a median duration of response of around 1 year and a median overall survival that has not been reached.

What is most important is that these data will be used as a basis for an upcoming marketing authorization application at the EMA. What we are planning is to try to see if we are able to get this drug approved across Europe. 

Source: 

Ortiz-Maldonado V, Martinez-Cibrian N, Alserawan L, et al. Varnimcabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia in Spain (CART19-BE-02): A multicentre, single-arm, phase 2 trial. Lancet Haematol. Published online: February 3, 2026. doi: 10.1016/S2352-3026(25)00328-X