Preliminary observation of growth and pubertal development following CAR-T cell therapy for children with systemic lupus erythematosus.

Abstract

e14516 Background: Prolonged glucocorticoid and immunosuppressive therapy in systemic lupus erythematosus (SLE) children can cause a range of unique adverse effects, including impaired linear growth and disrupted pubertal development. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved initial efficacy in the treatment of lupus, potentially allowing for rapid discontinuation of chronic immunosuppression. Studies involving pediatric patients and examining the impact of CAR-T therapy on their growth and developmental outcomes remain scarce. Methods: Pediatric r/r SLE patients ( > age 10 years old) were allowed to enrolled in our clinical trial (NCT06947460), besides monitoring safety (primarily evaluated through dose-limiting toxicity) and the efficacy (SLEDAI, LLDAS, SRI-4) of CAR-T cell therapy for r/r SLE children, improvement of growth and pubertal development was monitored. Baseline height was measured in all patients before CAR-T cell infusion, followed by regular assessments at 3-month intervals post-treatment according to a predefined follow-up plan, assessed by the criteria of the Standard for Height Level Classification among Children and Adolescents Aged 7–18 Years (2018 Version). Pubertal development was also assessed using Tanner staging. Results: Between Jun 12 and Sep 20, 2025, 4 r/r SLE children were enrolled. All patients stopped glucocorticoids and immunosuppressants pre-infusion and remained drug-free. No DLTs occurred within 28 days after infusion. All patients experienced grade 1 CRS; 25% had grade 2 hematologic toxicity. No neurotoxicity was observed and all toxicities resolved with supportive care. As of 31 December 2025, all 4 patients completed efficacy assessments at months 1, 3, and 6. Remission rates were 75%/75%/75% (DORIS), 75%/100%/75% (LLDAS), and 75%/75%/75% (SRI-4). 1 patient had a grade 3 viral infection and fully recovered after hospitalization. SLEDAI and PGA scores decreased by 2–6 and 0.5–2 points, respectively. From drug discontinuation to 6 months after CAR-T infusion, all patients demonstrated catch-up growth. Compared with references, a part of patients exhibited reduced height prior to treatment discontinuation: the 12-year-old girl (144cm) was approximately 3cm below the expected height (147cm), and the 11-year-old girl (133cm) was about 1cm below the expected height (134cm). The remaining patients had heights within the normal range. Height gains ranged from +1cm to +20.5cm. All patients exhibited secondary sexual characteristics within normal Tanner stages, indicating no missed pubertal window. Conclusions: CAR-T cell therapy shows a favorable safety and efficacy profile for r/r SLE children. These data suggest it may mitigate growth and development toxicity associated with conventional immunosuppressive therapy, which is unique unmet need for pediatric SLE patients. Clinical trial information: NCT06947460 .