CAR T-Cell Therapy Appears Safe, Effective in Treating Some Autoimmune Disorders

Autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy appears to be safe and effective in the treatment of several autoimmune diseases, according to findings published last week in the New England Journal of Medicine.

In this case series, investigators in Germany evaluated 15 patients with severe autoimmune diseases: eight with systemic lupus erythematosus (SLE), three with idiopathic inflammatory myositis and four with systemic sclerosis. The patients received a single infusion of CD19 CAR T cells after preconditioning with fludarabine and cyclophosphamide. Investigators monitored patients' disease activity using various assessment tools tailored to their specific autoimmune conditions.

The median follow-up was 15 months. Among eight patients with SLE, all met the Definition of Remission in SLE (DORIS) criteria after 6 months. Long-term follow-up (up to 29 months) showed that SLE disease activity remained absent in all patients. Furthermore, all three patients with idiopathic inflammatory myositis had a major clinical response and normalization of creatine kinase levels after 3 months. Among patients with systemic sclerosis, global disease activity decreased in all four patients. All 15 patients successfully discontinued glucocorticoids and other immunosuppressive medications as of the final follow-up.

In addition, investigators performed analyses of B-cell subsets at baseline, 4 months and 12 months after CAR T-cell therapy. They found that the dynamics of CAR T-cell expansion and of B-cell ablation were highly consistent among patients despite differences in disease entities and previous treatments. The results also indicated that CD19 CAR T-cell therapy was effective independent of previous B-cell targeting by monoclonal antibodies.

According to authors, the data provide new evidence for the short- and long-term safety and efficacy of CD19 CAR T-cell therapy in autoimmune disease. They noted, however, that further controlled clinical studies are needed. “Even though it is premature to judge whether these patients are indeed cured from their autoimmune disease, CD19 CAR T cells at least appear to be able to achieve sustained disease- and drug-free remission,” the authors wrote.