A multidisciplinary Clínic-IDIBAPS team, part of the Clínic Barcelona Comprehensive Cancer Centre (4CB), has published phase 2 results of the CAR-T ARI-0001 (varnimcabtagene autoleucel) for treating adults with B-cell acute lymphoblastic leukemia (ALL) in The Lancet Haematology. Led by first author Dr. Valentín Ortiz Maldonado, hematologist at Clínic and researcher in the IDIBAPS Lymphoid Neoplasms Group, and last author Dr. Jordi Esteve, hematologist at the hospital and head of the IDIBAPS Myeloid Neoplasms Group, the study confirms the therapy's therapeutic potential.
Developed at Clínic-IDIBAPS, this CAR-T was approved by AEMPS as a non-industrial advanced therapy medicinal product for ALL and was the first therapy of its kind fully developed in Europe to gain regulatory approval. It also received PRIME designation from the EMA, providing enhanced support for high-priority advanced therapies.
Acute lymphoblastic leukemia and the role of CAR-T therapies
Acute lymphoblastic leukemia (ALL) is a blood cancer characterized by uncontrolled proliferation of lymphoblasts—immature immune system cells—that interfere with normal blood cell production. In adults with relapse or treatment resistance, therapeutic options are limited and outcomes are often poor.
CAR-T therapies involve modifying a patient's own T lymphocytes to recognize and destroy tumor cells. ARI-0001 targets the CD19 protein on the surface of B leukemic cells.
A multicenter study with patient-adapted administration
The study included 32 adult patients treated at nine hospitals within the National Health System. ARI-0001 (varnimcabtagene autoleucel) was administered in four staggered, fractionated doses designed to adapt to each patient's clinical condition and reduce risks from initial CAR-T cell expansion.
Results show this approach achieved deep responses in patients with few treatment options. 84% achieved complete remission with undetectable measurable residual disease (MRD) at day 28, rising to 87% complete remission within three months. 12-month overall survival was 80%, significant for this disease.
Regarding safety, cytokine release syndrome—a common CAR-T side effect—occurred in 73% of patients, but only 12% had severe cases. Severe neurotoxicity was rare (3%). Despite treating high-risk patients often with heavy tumor burden, toxicity was clinically manageable in the hospital setting.
A pioneering, collaborative public health project
ARI-0001's development and implementation exemplify exceptional collaboration among Spanish public institutions. The product resulted from extensive multidisciplinary work across Hospital Clínic services including Hematology, Immunology (led by Dr. Manel Juan), Apheresis in Hemostasis and Hemotherapy, and Clinical Pharmacology, among others.
The clinical trial received priority funding from the Instituto de Salud Carlos III (ISCIII). However, the study's national scope and patient volume required extraordinary effort: multiple autonomous communities provided additional funding to enable patient enrollment. This demonstrates the public system's commitment to advanced therapies.
Clínic-IDIBAPS advanced therapy development is supported by ”la Caixa” Foundation, which has decisively contributed to the necessary infrastructure for innovative therapies like ARI-0001.
Toward greater accessibility of advanced therapies
CAR-T ARI-0001 results from a public system-led innovation model integrating research, care, and knowledge transfer. Promoted by the Clínic Barcelona Comprehensive Cancer Centre, this approach can improve access to advanced therapies and strengthen public research's role in new treatments.
The authors note the need to study ARI-0001 in earlier disease stages and explore its potential in other hematological malignancies.
Study reference:
Ortiz-Maldonado V, Triana-Mosquera A, Magnano 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. The Lancet Haematology. 2026. doi:10.1016/S2352-3026(25)00328-X.
