For most patients with autoimmune rheumatic disease, remission still depends on ongoing therapy.
Dr. Vikas Majithia is the chair of the Division of Rheumatology at Mayo Clinic in Jacksonville, Florida. He delivered The Menopause Society/Pfizer Wulf H. Utian Endowed Lecture, 'A new era in therapy for autoimmune diseases: chimeric antigen receptor T-cell therapy brings the prospect of ‘CURE’ within reach,' at The Menopause Society 2026 Annual Meeting, held October 20 to 24 in San Diego, California. He described how chimeric antigen receptor (CAR) T-cell therapy may allow an immune reset.
Dr. Majithia began with his patient, a 32-year-old Navy aviator who was medically discharged after a lupus diagnosis and later developed lupus nephritis. Despite glucocorticoids and 6 standard-of-care therapies, she had active lesions, arthritis, and persistent kidney inflammation. 'At that point, we really had only one thing left that we could offer, and that was chemotherapy,' he said.
Lupus is a leading cause of death among Black and Hispanic women aged 15 to 34 years, and current immunosuppressive therapies fail to achieve durable remission in up to half of the patients with complex, refractory disease. 'We throw a lot of treatments at them, and they don't respond,' he noted.
Why B cells may be the target for CAR T-cell therapy in autoimmune disease
B cells drive a self-perpetuating cycle in autoimmunity, he explained. B-cell–directed monoclonal antibodies can clear them from circulation, but responses remain below 50%. 'They are hiding in various places, and they continue to perpetuate the disease,' he said.
CAR T-cell therapy equips a patient's own T cells to target CD19-positive B cells, including those hiding in tissues. The cells expand rapidly, clear pathologic B cells, and then disappear, leaving a few memory cells as a 'living drug.' The immune system then reconstitutes from normal precursors, enabling a potential immune reset.
Pooled data from phase 1 trials and case series include 192 patients with lupus followed for up to 48 months. Most remained free of disease activity, with relapse in 3 patients. Serious side effects were few and reversible, although some serious infections occurred.
His patient received CD19-targeted CAR T-cell therapy in July 2024. Her lupus disease activity score fell to 0, she remained in drug-free remission at 27 months, and she was cleared to return to work as an aviator.
Open questions about CAR T-cell therapy through a menopause lens
For these young patients, Dr. Majithia said, the goal is to get them through menopause. Long-term fertility and gonadal effects of CAR-T therapy remain unknown. He also raised questions about whether declining estrogen levels during the menopause transition influence CAR T-cell efficacy, how the therapy affects ovarian function and the timing of menopause, and whether menopause status modifies toxicity risk. 'We don't know the answer to those questions,' he said.
Dr. Majithia concluded that there is 'a huge potential and great excitement for cellular therapies in autoimmune diseases.' Toxicities need careful monitoring, he said, and cost and access may be obstacles.
CAR, chimeric antigen receptor.