Background/Purpose: CD19-targeting CAR-T-cells showed remarkable improvements in autoimmune diseases including refractory lupus erythematodes (1,2) and inflammatory myopathy (3). Moreover, first data of a patient with diffuse Systemic Sclerosis (SSc) were recently reported (4). Here we present 6 months follow up data of the first three patients with severe diffuse SSc who received CAR-T-cell treatment.

Methods: T-cells were acquired by peripheral blood apheresis and transfected with a lentiviral vector encoding a CAR against CD19 (Miltenyi Biotec) using the CliniMacs Prodigy system (Miltenyi Biotec). Infusion of CAR-T-cells was performed upon lymphodepletion with fludarabine (25 mg/m² on days -5, -4, -3) and cyclophosphamide (1g/m2 on day -3, 50% dose reduction in patient 3 due to renal insufficiency) as single infusion. Immunosuppression was stopped before CAR-T-cell infusion. Outcomes were assessed before baseline and 6 months after CAR-T-cell infusion.

Results: Three SSc patients were treated with CAR-T-cells with a follow up of 6 months: patient 1 (male, baseline data: 60 yrs, disease duration 2 years (first non-Raynaud symptom), mRSS 24, myocardial- and lung fibrosis, anti RNAP3-antibodies), patient 2: male, 37 yrs, mRSS 27, disease duration 1.5 yrs, lung- and myocardial fibrosis, digital ulcerations (DU), anti-Scl70 antibodies) and patient 3 (female,38 yrs, disease duration 1.5 yrs, mRSS 32, scleroderma renal crisis, DU, anti-Scl70 antibodies). All patients had failed state of the art SSc treatments. The CAR-T-cell procedure was well tolerated: Patient 1 developed mild CRS (grade I; fever) and an episode of respiratory tract infection three months after CAR-T infusion, treated outpatient with antibiotics. B-cells were completely absent in peripheral blood within 7 days after CAR-T cells administration in all patients. ANA titres were reduced by 10-fold in patients 2 and 3, patient 1 converted to negative ANA status within 3 months and anti-RNAP III antibodies turned negative. mRSS improved in all three patients until six-months follow up (median 6 points (5-7)). 2 patients suffered from multiple digital ulcerations despite bosentan- treatment before CAR-T cells, which were no longer detectable on follow up. All patients reported improvement of hand function (median reduction of Cochin Hand function scale of 8 points (8-20). Improvement of HAQ-DI ranged from 0.5 to 1.38 points and of EUSTAR activity from 3.62 to 4.37 points. Lung function parameters remained stable in patients 1 and 3 and improved in patient 2 (FVC increase by 390 ml (8%)). Myocardial ⁶⁸Ga-FAPI-04-uptake declined in patients 1 and 2 by 30% and 35% respectively. B-cells recurred after 84 days in patient 1 and 2 without signs of disease activity.

Conclusion: These data on the first three SSc patients receiving CD19 CAR-T cell treatment show that the procedure is well tolerated and can lead to stabilization of SSc disease activity without additional immunosuppression on 6 months follow up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/6-months-follow-up-data-of-systemic-sclerosis-patients-treated-with-cd-19-targeting-car-t-cells/