CD19 CAR-T cells show safety and clinical responses in the CASTLE trial

The phase 1/2a CASTLE study treated 24 patients with refractory SLE, SSc or IIM using autologous CD19 CAR‑T cells; the trial met its primary safety endpoint and most patients met predefined 6‑month efficacy criteria.

CASTLE reports phase 1/2a results of autologous CD19 CAR‑T cell therapy for patients with severe, treatment‑refractory systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM). The study enrolled 24 patients between July 2023 and January 2025 and combined safety as the primary endpoint with clinical efficacy at six months as a key secondary endpoint. Investigators also assessed immune effects, including B cell depletion, changes in autoantibodies and B cell compartment composition. Follow‑up data extend to a median of about 13 months. Key facts: - Twenty‑four patients (10 SLE, 9 SSc, 5 IIM) received a single infusion of autologous CD19 CAR‑T cells in the CASTLE trial. - The trial met its primary safety threshold with only one recorded dose‑limiting toxicity in phase 1 and no predefined toxicity events in phase 2a; most treatment‑related adverse events were low‑grade or resolved. - At six months, predefined disease‑specific efficacy criteria were met for the majority of patients (overall response reported as 87.5% in phase 2a), and no relapses were observed during a median follow‑up of 13 months. - Treatment produced rapid B cell depletion followed by reconstitution with a predominance of naive B cells and reductions in several disease‑associated autoantibodies; some patients required immunoglobulin replacement, and one patient experienced persistent grade 3 kidney impairment as a continuing serious adverse outcome. Summary: CASTLE reports that a single administration of autologous CD19 CAR‑T cells met predefined safety limits and produced clinical responses across three severe autoimmune diseases, with measurable immune changes including B cell depletion and reduced autoantibodies. Most patients remained drug free during follow‑up, though one serious adverse event with lasting kidney impairment was recorded. Undetermined at this time.