Anti-CD19 CAR-T (Fuda Tumor Hospital of Guangzhou Fuda Medical )

To present a successful case study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a patient with relapsing granulomatosis with polyangiitis (GPA).

A 69-year-old male patient suffering from relapsing GPA refractory to standardized immunosuppression underwent an experimental therapy involving CD19-targeting CAR T cells. The conditioning regimen consisted of fludarabine and cyclophosphamide. Follow-up intervals scheduled at 1 to 3 months’ intervals, incorporated evaluations of the BVAS, CT scans of the lungs, CRP, peripheral white blood cell count (WBC), lactate dehydrogenase, ANCA, immunoglobulin levels, post-CAR T-cell treatment surveillance including (CAR)-lymphocyte counts.

The patient was diagnosed with GPA involving the lungs in 2019. He showed a relapsed refractory disease course in spite of treatment with rituximab, cyclophosphamide, avacopan, azathioprine, leflunomide and prednisolone. At presentation for CAR T-cell treatment, the BVAS was 14, inflammation markers were elevated, and pulmonary infiltrates were visible on the CT scan. CAR T-cell therapy was well-tolerated with no cytokine release syndrome (CRS) or neurotoxicity, and led to rapid improvement of clinical condition, as well as radiological and laboratory test results. CAR T cells expanded with a transient peak but were not anymore detectable in the peripheral blood around day 90. In line the significant B-cell depletion and hypogammaglobulinemia observed post-treatment showed gradual recovery. At the latest follow-up of 12-months post-treatment, the patient is in complete remission without further medication.

CD19-targeted CAR T-cell therapy was safe and efficacious in a patient with relapsed and refractory GPA. CAR T-cell therapy has the potential to transform disease management and improve long-term outcomes for affected patients.

CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has advanced treatment strategies for severe autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis, and idiopathic inflammatory myopathy. Data regarding side-effects are mostly generated from patients with malignancies, but little is known about autoimmune disease-specific adverse events. This study aimed to describe autoimmune disease-specific adverse events that occur with CAR T-cell therapy.

In this observational study, patients of any age with autoimmune disease receiving CD19-targeting CAR T-cell therapy in two centres in Germany with a follow-up of at least 30 days were assessed for local organ-specific reactions occurring after CAR T-cell infusion. Observed reactions were documented according to localisation, time of onset, and duration, and were graded for severity (grade 1: spontaneous resolution; grade 2: glucocorticoid treatment due to symptoms lasting >1 week or presence of relevant inner organ involvement; grade 3: prolonged or new hospitalisation; grade 4: intensive care treatment). People with related lived experience were involved in the study design and implementation.

Between March 1, 2021, and Oct 31, 2024, 39 patients with autoimmune disease were treated with CD19-targeting CAR T cells (20 with SLE, 13 with systemic sclerosis, six with idiopathic inflammatory myopathy). 25 (64%) patients were female and 14 (36%) were male. Median age was 36 years (IQR 22-44). 54 local reactions, which we termed local immune effector cell-associated toxicity syndrome (LICATS), were recorded, affecting 30 (77%) patients with a median time of onset of 10 days (IQR 9-21) from CAR T-cell infusion and a median duration of 11 days (5-14). LICATS exclusively occurred during the B-cell aplasia phase and only involved organs previously affected by the respective autoimmune disease. The most frequently affected organs were the skin (19 [35%] of 54) and the kidneys (12 [22%]). Most cases of LICATS were mild (grade 1: 35 [65%]; grade 2: 16 [30%]). Only three cases were grade 3. All events of LICATS resolved without sequelae.

LICATS is a new form of toxicity in patients with autoimmune disease receiving CD19-targeting CAR T-cell therapy, most likely based on the cleansing of immune cells from the affected organs. It is self-limited, organ-specific, and usually mild in its intensity.

Deutsche Forschungsgemeinschaft (DFG), German Cancer Aid, Bundesministerium für Bildung und Forschung, European Union, Staedtler Foundation, Lupus Research Alliance, and donations from the Bendel family and the Bleyl family.