CHICAGO—At a Sunday, Oct. 26, session of ACR Convergence, Joan T. Merrill, MD, overviewed the current research landscape of chimeric antigen receptor (CAR) T cell therapies for systemic lupus erythematosus (SLE), raising important scientific questions about these emerging treatments. Dr. Merrill is the director of clinical projects in the Arthritis & Clinical Immunology Research Program at Oklahoma Medical Research Foundation, Oklahoma City.
Background
In CAR T therapy, a patient’s T cells are removed and genetically modified to act as immune modulators. Most of those studied in SLE to date target an antigen found on B cells, CD19. After receiving chemotherapy treatment (usually cyclophosphamide and fludarabine), the patient is reinfused with their own modified T cells. In early studies, this has led to rapid and deep reductions in circulating B cells and B cell tissue reservoirs, with consequent impressive improvement in SLE symptoms, even as the B cells repopulate.1,2
Dr. Saira Sheikh
Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic at Chapel Hill, introduced the session. “What began as a targeted approach for B cell malignancies is rapidly evolving into a precision tool, potentially capable of inducing deep, treatment-free remission in refractory lupus. The excitement is palpable, but there is much to learn.”
Throughout her lecture, Dr. Merrill also maintained a careful balance of hopeful enthusiasm and healthy, rigorous skepticism with respect to these therapies.
Efficacy
Dr. Joan Merrill
Although the area is still incredibly young, multiple centers have now administered CAR T therapies in SLE patients. Dr. Merrill discussed results of a recent systematic review of 16 case series studies of CAR T in SLE, with 145 patients in total. Protocols differed somewhat and included 12 autologous and four allogeneic CAR T studies; 13 studies targeted the marker CD19 and three targeted both CD19 and B-cell maturation antigen (BCMA; a marker associated with plasma cells).1
From a baseline median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of 13.1, the median score dropped to 2.3 after six months and 1.4 after 12 months. Looked at another way, 84% achieved drug-free remission, and 89% had low disease activity (as quantified by Lupus Low Disease Activity State criteria).1
“These are phenomenal results,” said Dr. Merrill, “really remarkable.”
Side Effects
Dr. Merrill put in context some of the key adverse events in patients receiving CAR T therapy for SLE, many of which have been previously described from the oncology literature. However, fully understanding the nature of these events is challenging, as they might result from CAR therapy itself, from the chemotherapy used as part of CAR T protocols, from other potent treatments for SLE or from actual disease symptoms.
