All Grand Rounds
Peer Discussion
CAR-T Cell Therapy for Refractory Lupus and Autoimmunity
Early case series of CD19-directed CAR-T cell therapy in refractory lupus and other autoimmune diseases have reported drug-free remissions, but the approach is emerging and investigational and is not FDA approved for autoimmune disease.
Recording
The discussion
Background. B cells and plasmablasts drive many autoimmune diseases, but antibody-based B-cell depletion with rituximab often leaves tissue-resident B cells untouched. CD19-directed chimeric antigen receptor (CAR) T cells, developed for B-cell cancers, can achieve much deeper depletion, including in lymphoid tissue.
What the data showed. After a first case report in 2021, Mackensen and colleagues in Erlangen reported in Nature Medicine that five patients with refractory SLE, including lupus nephritis, achieved drug-free remission after CD19 CAR-T therapy. B cells returned after a few months with a naive phenotype, yet remission persisted. A subsequent NEJM case series from the same group extended follow-up and included patients with idiopathic inflammatory myositis and systemic sclerosis, with sustained responses and mostly low-grade cytokine release syndrome. These are small, uncontrolled series from expert centers, and patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide.
How it may change practice. Not yet. CAR-T therapy for autoimmune disease is available only within clinical trials. Its importance is conceptual: deep B-cell depletion may reset the immune system rather than suppress it, which challenges our assumption that autoimmune disease requires lifelong therapy. Our role now is to identify patients with truly refractory disease and refer them to trial centers when appropriate.
Open questions. How durable are remissions over many years? What are the long-term risks, including infection, hypogammaglobulinemia, effects on fertility from conditioning chemotherapy, and the secondary T-cell malignancies reported with approved CAR-T products, which prompted FDA safety labeling? Can allogeneic or in vivo CAR-T, or bispecific T-cell engagers, deliver similar benefit with less toxicity and cost? Which diseases and which patients should be first?
Key takeaways
• CD19 CAR-T therapy has produced drug-free remissions in small series of refractory SLE, myositis and systemic sclerosis.
• The evidence comes from uncontrolled case series; randomized and long-term data are lacking.
• CAR-T therapy for autoimmune disease is investigational and available only through clinical trials.
• Safety questions include conditioning chemotherapy, infection, fertility and secondary malignancy.
Questions for peers
1. Which of our patients would meet a reasonable definition of truly refractory disease for CAR-T referral?
2. How should we discuss investigational therapy with hope but without overpromising?
3. Would bispecific T-cell engagers or allogeneic CAR-T be preferable as first-line deep B-cell depletion strategies?
4. What would convince us that a remission is a true immune reset rather than prolonged suppression?
References
1. First CAR-T for SLE: Mougiakakos D et al. N Engl J Med 2021. First report of CD19 CAR-T therapy inducing remission in a patient with severe SLE. PubMed
2. CD19 CAR-T in refractory SLE: Mackensen A et al. Nat Med 2022. Five patients with refractory SLE achieved drug-free remission after CD19 CAR-T therapy. PubMed
3. CD19 CAR-T in autoimmune disease: case series: Müller F et al. N Engl J Med 2024. Extended follow-up in SLE, myositis and systemic sclerosis with sustained responses. PubMed
At a glance
Format
Peer Discussion
Reviewed by Farhan Tahir, MD, FACR
Join the conversation
Clinicians can suggest a topic, share a perspective or volunteer to present on Autoimmunity in Focus.
Peer education for clinicians. Not medical advice for individual patients.
THE YOUTHFUL RHEUMATOLOGY BRIEF
Inflammation science, translated for you.
New studies, new treatments and practical living-well insights for autoimmune and inflammatory disease, explained in plain language by Dr. Tahir. About twice a month. Education only, never sales pitches.
Your privacy matters. We will never sell, rent or share your email or personal information. We use it only to send this newsletter, and you can unsubscribe anytime. Educational content only, not medical advice.