Hormone levels of female patients with SLE after anti-CD19 CAR T-cell treatment do not indicate a signal of impaired ovarian reserve
Ann-Christin Pecher, Jörg Henes, Melanie Henes, Claudia Lengerke, Wolfgang Bethge, Andreas Wirsching, Tobias Rothe, Fabian Müller, Andreas Mackensen, Georg Schett, Melanie HagenAbstract
Objectives
Women with systemic lupus erythematosus (SLE) are at increased risk of infertility due to disease activity and exposure to gonadotoxic therapies. Anti‑CD19 chimeric antigen receptor (CAR) T‑cell therapy has recently been shown to induce durable, drug‑free remission in refractory SLE; however, its effects on ovarian function remain unknown. We assessed longitudinal changes in reproductive endocrine markers to evaluate the impact of CAR T‑cell therapy on ovarian reserve and hypothalamic–pituitary–ovarian (HPO) axis function.
Methods
Women with severe, treatment‑refractory SLE receiving autologous anti‑CD19 CAR T‑cell therapy (Miltenyi Biomedicine) in conjunction with standard lymphodepletion at two tertiary care centres were studied. Anti‑Müllerian hormone (AMH), estradiol (E2), progesterone, follicle‑stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were measured at baseline and 12 months after therapy. Blood samples were obtained independent of menstrual cycle phase. Paired statistical analyses were performed.
Results
Thirteen women were included; median age at CAR T‑cell therapy was 27 years. AMH levels were stable (1.54 ng/mL [IQR 0.64–3.15] vs 2.14 ng/mL [0.63–3.26]; p = 0.886). E2 (243 pmol/L [186–346] vs 484 pmol/L [277–829]; p = 0.339) and progesterone (0.90 nmol/L [0.80–0.90] vs 1.80 nmol/L [0.90–3.40]; p = 0.054) showed substantial variability without significant longitudinal change. FSH increased modestly (6.60 IU/L [4.00–7.90] vs 7.20 IU/L [4.50–9.90]; p = 0.033) without a concomitant decline in AMH. LH (6.10 IU/L [5.10–12.90] vs 7.00 IU/L [5.00–12.90]; p = 0.946) and prolactin (10.0 µg/L [8.0–10.0] vs 8.0 µg/L [5.0–9.0]; p = 0.123) remained stable.
Conclusion
Anti‑CD19 CAR T‑cell therapy including standard lymphodepletion showed no signal of impaired ovarian reserve, as assessed by AMH and hormone profiles. Observed hormonal changes, including FSH, should be interpreted with caution given study limitations.