CD19-targeted CAR T cells in refractory antisynthetase syndrome

Idiopathic inflammatory myopathies are a group of rare, immune-mediated diseases that primarily affect the skeletal muscle but can also involve other organs such as the lungs, skin, and joints.1 Antisynthetase syndrome comprises a major cluster of such diseases and is characterised by the development of adaptive immune responses against various tRNA synthetases, including those for histidine (forming anti-Jo-1 antibodies), tyrosine (anti-PL7), alanine (anti-PL12), glycine (anti-EJ), isoleucine (anti-OJ), asparagine (anti-KS), phenylalanine (anti-Zo), and threonine (anti-HA).2 Histopathology studies of patients with antisynthetase syndrome have shown the presence of B cells and plasmablasts located adjacent to T cells in the affected muscles,3 and the condition is also associated with changes in the profile of peripheral B cells.3 In accordance with these findings, B-cell-depleting therapy with rituximab was efficacious in a subset of patients with antisynthetase syndrome, supporting the pathogenic role of autoreactive B cells.4 Antisynthetase syndrome can be refractory despite several treatment options—including glucocorticoids, intravenous immunoglobulins, T-cell-targeting drugs, and B-cell-targeting drugs—and is therefore associated with increased mortality.5 Considering the pathophysiology of antisynthetase syndrome, treatment with chimeric antigen receptor (CAR) T cells that recognise CD19⁺ B cells might be useful in refractory forms of the disease. Increased creatinine kinase concentrations and myalgia have been reported as part of cytokine release syndrome.8 After this short worsening, the patient markedly improved in physical function according to all International Myositis Assessment and Clinical Studies Group core set measures (figure F, appendix p 1). Regarding safety, the patient developed a fever (38–39°C, with no effect on blood pressure) 1–3 days after CAR T-cell treatment, which was treated with paracetamol and 3 × 720 mg tocilizumab.