Case study of resecabtagene autoleucel in a subject with diffuse cutaneous systemic sclerosis treated in the RESET-SSc trial.

Under compassionate use, CAR T cells have elicited durable remissions in patients with refractory systemic sclerosis (SSc). Here, we report on the safety, efficacy, and correlative data of the first SSc subject treated with a fully human CD19-CART cell therapy (resecabtagene autoleucel) in the RESET-SSc trial (NCT06328777). Nine days post-infusion, the subject experienced a brief grade 2 episode of cytokine release syndrome that resolved promptly with intravenous hydration and indomethacin. Immune-effector-cell-associated neurotoxicity syndrome was not observed. Seven days post-infusion, the subject experienced a brief grade 4 episode of neutropenia that resolved rapidly with a single dose of colony-stimulating factor. Despite discontinuation of all immunosuppressants since infusion, over the 9-month period post-infusion, the subject's skin thickness decreased, pulmonary function improved, and nailfold vasculature improvement was observed. Following infusion, B cells were depleted both in the periphery and within secondary lymphoid tissue. B cell aplasia was observed by day 13 post-infusion. Furthermore, serum BAFF was highly elevated. B cell repopulation began 8 weeks post-infusion, with cells exhibiting a transitional naive phenotype. Autoantibodies to RNA polymerase III decreased to undetectable levels. The infusion product consisted of predominantly CD4+ T cells, and both CD4+ and CD8+ populations had similar in vitro activity. Post-infusion, rese-cel expansion peaked at 13 days. These data detail the safety, efficacy, and pharmacodynamics of rese-cel in the first SSc subject.