Challenges and Opportunities for CAR T-Cell Therapies to Treat Autoimmune Rheumatic Diseases Authors: Eric Morand, MD, PhD; David Simon, MHBA; Fabian Müller, MD; Gerhard Krönke, MD, MHBA

https://www.medscape.org/viewarticle/1003043?sso=true&uac=148436CN&src=mkmcmr_reeng_recap_mscpedu_activity thank you for your recent participation in the activity: Challenges and Opportunities for CAR T-Cell Therapies to Treat Autoimmune Rheumatic Diseases Below are some key learning points to help reinforce the impact of this activity. ☑ B cells drive rheumatic autoimmune diseases (ADs) through both antibody-dependent and antibody-independent mechanisms. Although traditional depletion therapies such as rituximab show variable efficacy, CAR T-cell therapy, a treatment established for B cell-derived malignancies, offers a new approach for deep, sustained B-cell depletion, with potential for immune reset. ☑ A recent case series showed that patients with severe ADs, such as systemic lupus erythematosus, myositis, and systemic sclerosis achieved sustained, drug-free remission with cluster of differentiation (CD)19-targeted CAR T-cell therapy. This remarkable efficacy appears to be driven by immune reset involving deep B-cell depletion and subsequent reconstitution, autoantibody clearance, and interferon suppression. ☑ Safety data show a lower toxicity of CD19-targeted CAR T-cell therapy for ADs than for hematologic malignancies. Although severe cytokine release syndrome and neurotoxicity are less frequent, infections and emerging events, such as local immune effector cell-associated toxicity syndrome (LICATS), may occur and warrant vigilance. ☑ Although CAR T-cell therapy was initially reserved for patients with severe, refractory diseases, eligibility is evolving with growing data supporting broader use in ADs. Severely reduced heart function remains a key contraindication, but low lung or kidney function is increasingly acceptable with careful management. ☑ To effectively manage the complexities of delivering CAR T-cell therapy and the underlying AD, close collaboration between rheumatologists and hematologists is essential throughout the entire process, from patient assessment to long-term follow-up.