CAR-T Cells: Are We Closer to Drug-Free Remission Than We Think?

A Trial Worth Reading

Müller et al. evaluated 15 patients with severe, refractory systemic lupus erythematosus (SLE, n=8), idiopathic inflammatory myositis (IIM, n=3) and diffuse cutaneous systemic sclerosis (SSc, n=4).¹ All patients had previously had an inadequate response to at least two prior immunosuppressants (median, 5; range, 2–14 prior treatments). All SLE patients had active skin and renal disease (biopsy-confirmed Class III/IV lupus nephritis). All IIM patients had active lung and muscle disease. All SSc patients had active lung and skin disease. Six patients were men and nine were women. Patient ages ranged from 20–60 years. Disease duration ranged from one to 20 years.

Each patient received a single infusion of CD19 CAR-T cells after preconditioning with fludarabine and cyclophosphamide. Every single patient achieved a significant decrease in disease activity scores and/or remission, and all patients successfully stopped glucocorticoids and all other immunosuppressive medications as of the final follow-up visit (median 15 months; interquartile range 7–19 months).

More specifically, all eight SLE patients met Lupus Low Disease Activity State (LLDAS) criteria and had Definition of Remission in SLE (DORIS) remission after six months. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were zero, and British Isles Lupus Assessment Group (BILAG) status at follow-up showed resolution of SLE in all major disease categories after six months. Up to 29 months out, SLE disease activity remained absent in all patients. Anti-dsDNA antibodies disappeared and remained negative, complement factor C3 levels normalized, and proteinuria resolved during the entire observation period.

All three IIM patients had an ACREULAR Total Improvement Score major clinical response, normalization of creatine kinase (CK) levels and muscular function after three months, and improvement of extramuscular disease activity.

All four patients with SSc saw decreases in the European Scleroderma Trials and Research Group (EUSTAR) activity index (median change –4.2 points, interquartile range –4.7 to –2.3), as well as a decrease in modified Rodnan skin scores (median change –9, interquartile range –17 to –7).

Adverse effects of CAR-T cell therapy were minimal and tolerable. No patients died. No moderate- or high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. There were no prolonged bone marrow toxic effects. Mild infections occurred, with only one patient requiring hospital admission (for a diagnosis of pneumonia, which resolved with antibiotics). New-onset hypogammaglobulinemia was uncommon.

Interview with an Expert

Dr. Frigault

Dr. Frigault was kind enough to sit down and let me pick his brain about the ins and outs, as well as the future, of cell therapy in rheumatic disease.