Safety and Efficacy of CD19 CAR-T Cells for Refractory Systemic Sclerosis: A Phase I Clinical Trial

Highlight of 2023: CAR T cells driving precision therapy for autoimmune disease

“…Therefore, anti‐BCMA CAR T cells may represent a promising approach for autoimmune diseases where pathogenic autoantibodies are derived from CD20‐negative plasma cells. Given that autoimmune diseases are highly heterogenous and pathogenic autoantibodies likely derive from multiple sources, studies are currently underway to use combined targeting of CD19 and BCMA CAR T cells 11,12 . However, these treatments will require caution, as seven (58%) of the patients treated with anti‐BCMA CAR T cells developed infections and all patients developed a low‐grade CRS 4 …”

Potential and pitfalls of repurposing the CAR-T cell regimen for the treatment of autoimmune disease

“…Immunodepletion was achieved with total body irradiation and this was shown to improve effectiveness of CAR-T treatment. Subsequently, in 2022, a small phase I trial of CD19-targeted CAR-T cells in 5 patients with SLE was reported,22 followed by results from a combination of CD19 and BCMA-targeted CAR-T cells in 12 patients with refractory SLE,23 a small trial of 3 patients with refractory lupus using a different CD19 CAR-T construct24 and expansion of the original study to 3 additional patients with SLE 25. Notably, all patients were taking immunosuppressants or anti-B cell antibodies and were refractory to these conventional treatments prior to onset of CAR-T cell therapy.…”

“…A second consideration is the extensive reports of adverse effects reported in patients with B cell malignancies treated with CAR-T cell therapy, including immune-related effector cell neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS). While only a few cases of suspected ICANS with limited clinical impact have been reported in patients with SLE treated with CAR-T therapy to date, CRS was reported in most patients with refractory lupus23 24 but appears to be less frequent in the patients with less advanced disease 22. Whether this relates to the CAR construct employed or the nature of the patient’s disease status is unknown, and will require additional experience to evaluate the risk:benefit ratio.…”