Varnimcabtagene autoleucel (var-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved in Spain for the treatment of adults with acute lymphoblastic leukemia (ALL), induced a complete response with undetectable measurable residual disease (MRD) in nearly 85% of patients who received at least one fraction of treatment.
Valetín Ortiz-Maldonado, MD, of the Hospital Clínic de Barcelona in Spain, and colleagues published their findings in The Lancet Haematology.
Var-cel was approved in 2021 in Spain for patients aged 25 years and older with relapsed or refractory B-cell precursor ALL.
The multicenter, single-arm, phase 2 study enrolled 38 patients (median age, 40 years) from nine academic centers in Spain between May 19, 2021, and July 6, 2023.
Patients received intravenous fludarabine 30 mg/m2/day plus cyclophosphamide 300 mg/m2/day, both for three days, followed by intravenous fractionated var-cel infusions at the following dose levels:
- 1×106CAR T cells/kg
- 3×106CAR T cells/kg
- 6×106CAR T cells/kg
- 0×106CAR T cells/kg
Among those enrolled, 33 patients (87%) initiated lymphodepleting chemotherapy, and 32 (84%) received at least one var-cel fraction.
Median follow-up from infusion was 8.6 months, and the study met its primary endpoint. Treatment-related adverse events occurred in most patients (n=31; 94%).
The most common grade ≥3 adverse events were neutropenia (n=15; 45%), thrombocytopenia (n=7; 21%), anemia (n=5; 15%), and CRS (n=4; 12%). One patient experienced immune effector cell-associated neurotoxicity syndrome and cerebral edema, and two patients experienced immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, one of which resulted in death after protocol violation due to infusion during uncontrolled sepsis.
The researchers concluded that these findings “[support] fractionated dose escalation as a strategy that preserves activity, limits acute toxic effects, and supports a hospital-based approach that could expand access to CAR T-cell therapy.”
Var-cel is not approved by the US Food and Drug Administration.
Reference
Ortiz-Maldnado 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. 2026:S2352-3026(25)00328-X. doi:10.1016/S2352-3026(25)00328-X
