Team: B-Cell Busters

Base article: Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease – A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. PMID: 38381673.

Authors: Vanderbilt Rheumatology Fellowship Program

1. Yash Pershad, medical student, Vanderbilt University School of Medicine
2. Genessis Maldonado, MD, Fellow, Division of Rheumatology and Immunology, Vanderbilt University Medical Center
3. Tyler Reese, MD, Assistant Professor of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center

Team Overview: 

CAR T-cells just pulled off the biggest cross-division upset in rheumatology history. After revolutionizing the oncology league, these engineered cellular superstars crossed over to autoimmunity with style.

In this groundbreaking series, 15 players with refractory autoimmune disease (8 SLE, 3 myositis, 4 systemic sclerosis) who had struck out with conventional therapies got drafted into the CAR T-cell program. The results? Nothing but net—every single patient broke free from immunosuppressive drugs and scored long-term remission with manageable side effects.

What makes this squad special isn’t just their full-court press targeting B cells. Unlike other B-cell depleting veterans like rituximab, these CD19 CAR T-cells take down both B cells and plasmablasts. These T-cells have hustle and heart—they dive straight into the tissues and eliminate targets without waiting for backup from other immune system teammates. By deploying this deep bench of CD19-targeted CAR T-cells, they don’t just temporarily put autoimmune B cells in the penalty box like rituximab—they completely retool the immune roster, potentially leading to long-term tolerance. Their defensive IQ is off the charts—they preserve those crucial vaccine-memory plasma cells while eliminating the troublemakers. That’s the kind of smart, selective defense that wins championships.

The study evaluated the efficacy and safety of this game-changing therapy using disease-specific assessment tools. For systemic lupus erythematosus (SLE), disease activity was measured using the SLEDAI-2K score. Idiopathic inflammatory myositis (IIM) was assessed through serum creatine kinase levels, the Manual Muscle Test-8 (MMT-8), and the ACR-EULAR Total Improvement Score. In systemic sclerosis (SSc), disease severity was monitored using the modified Rodnan skin score (mRSS). Secondary endpoints included tracking the duration of clinical remission, persistence of CAR T cells, and incidence of adverse events, ensuring a comprehensive evaluation of the therapy’s long-term impact.

Admittedly, it is still early in the season with only 15 players on the roster—some may call this a fluke from a small-market team. But the implications for future patients are undeniably championship-caliber. CAR T-cell therapy represents a paradigm shift with the potential to revolutionize how we manage autoimmune disease.

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