OP0027 LONG-TERM SAFETY AND EFFICACY OF CAR-T CELL TREATMENT IN SEVERE AND TREATMENT REFRACTORY AUTOIMMUNE DISEASE

Background:

Autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM) and systemic sclerosis (SSc) often require long-term immune suppression. In some cases, the disease can be severe, progressive and does not adequately respond to standard immunosuppressive drug treatment. We and others have previously shown that administration of autologous CD19 chimeric antigen receptor (CAR) T cells can induce remission or at least major improvement in patients with SLE, IIM and SSc. Resetting aberrant autoimmunity in these diseases through deep depletion of B cell is a potential strategy for achieving sustained drug free remission in these diseases.

Objectives:

To investigate the long-term safety and efficacy of autologous CD19 CAR T cell therapy in in patients with SLE, IIM and SSc.

Methods:

CD19 CAR-T cells were prepared from leukapheresis specimen after enrichment of T cells and transfection with MB-CART19.1 lentiviral vector (Miltenyi). Cells were expanded for 12 days and 1 million CAR T cells/kg body weight were administered as a single intravenous infusion after standard conditioning therapy with 1g/m2 cyclophosphamide and 3x 25 mg fludarabine, as described previously [1,2]. Safety parameters, including cytokine-release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), myelotoxicity and infections, were recorded up to 3 years post CAR-T cell infusion. Efficacy was assessed using the Definition of Remission in SLE (DORIS), clinical response according to 2016 ACR/EULAR total improvement score (TIS) and the European Scleroderma Trials and Research Group (EUSTAR) activity index up to three years after CAR-T cell infusion.

Results:

Between February 2021 and May 2023, 15 patients (8 SLE, 4 SSc, and 3 IIM) were treated with CD19 CAR-T cells. Among them were ten women and five men. Patients were mostly young (median age 36 years; range [18-60] years). Median disease duration before CAR-T was 3 years [1-20]. All patients failed on multiple previous immune suppressive treatments (median 5 [2-14]). Median follow up time after CD19-CAR-T cell infusion was 18 months [8-32] with 5 patients followed-up over more than two years and 12 patients followed-up over more than one year. Regarding safety, no higher grade CRS was observed. Grade 1 CRS occurred in 8 patients, grade 2 CRS in 1 patient. Only a single grade 1 ICANS was observed. No acute myelotoxicity (grade 3 or 4 neutropenia or leucocytopenia > 28 days post CAR-T cell treatment) occurred. One patient, however, developed late-stage grade 4 neutropenia 120 days after CD19CAR-T cell treatment, which resolved upon G-CSF treatment. With respect to infections only one case of severe infection (pneumonia) requiring hospital admission was recorded, which required antibiotic treatment. All other infections were mild and mostly manifested as upper respiratory tract infections. With respect to efficacy, all SLE patients achieved DORIS remission, all IIM patients reached ACR/EULAR major response and all SSc patients improved in the EUSTAR activity index. Immunosuppressive therapy including glucocorticoids was completely stopped in all patients.

Conclusion:

This case series provides first evidence for the long-term safety and efficacy of CD19 CAR-T cell treatment in three different autoimmune diseases, providing the rationale for further controlled clinical trials.

REFERENCES:

[1] Mougiakakos D et al., CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med 2021;385:567-569. [2] Mackensen A. et al., Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus; Nat Med 2022 Oct; 28(10):2124-2132.

Acknowledgements:

NIL.

Disclosure of Interests:

None declared.