NEW YORK – An autologous CAR T-cell therapy originally designed for cancer led to complete drug-free remission in patients with lupus and other autoimmune diseases, according to a small study presented on Saturday at the American Society of Hematology's annual meeting in San Diego.
A team of researchers in Germany sought to establish whether a CD19-targeting CAR T-cell therapy, dubbed MB-CART19.1, that has previously been used to treat B-cell malignancies could also treat autoimmune diseases triggered by autoreactive B cells, such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc).
The goal was to test whether MB-CART19.1, manufactured using Miltenyi Biotec's CliniMACS Prodigy automated cell processing platform, could cure patients by "resetting" B cells driving such autoimmune diseases, said Fabian Mueller, head of the CAR T-cell unit at the University Hospital Erlangen and first author on the study abstract. He noted that at the start of the study, investigators proceeded cautiously as they were worried the process potentially could end up harming patients, since they were activating and then infusing T cells, which are often the cause of autoimmune diseases.
"We are talking about autoimmune diseases that are completely uncontrolled," he said during a press conference on Saturday to discuss the study findings.
In the study, researchers enrolled 15 patients with serious SLE, IIM, or SSc, who had previously failed multiple immunomodulatory therapies. They received a single infusion of the MB-CART19.1 CAR T-cell therapy through an expanded access program.
All 15 patients, who had stopped taking immunosuppressive drugs for their autoimmune diseases at data cutoff, saw their symptoms improve on CAR T-cell therapy at a median follow-up of 15 months post-treatment. After three months, all eight SLE patients reached complete remission and had no symptoms. They have maintained a score of zero on the Systemic Lupus Erythematosus Disease Activity Index.
"All lupus patients, as of today, don't show any symptoms, and they are completely free of treatment," Mueller said during a presentation at the meeting. "At this time, with limited follow-up, we say that CD19 CAR T achieves a lasting remission in SLE."
All three IIM patients also achieved remission at data cutoff, with normalization of creatinine kinase, a biomarker indicative of muscle inflammation and damage. Most SSc patients experienced an improvement in symptoms, according to a decrease of disease activity as measured by the European League Against Rheumatism's activity index.
The cell therapy appeared to have a favorable safety profile in these autoimmune disease patients, causing only low-grade inflammatory side effects due to cytokine-release syndrome (CRS). Four patients had grade 0, 10 patients had grade 1, and one patient had grade 2 CRS. Six of the 15 patients received Genentech's immunosuppressive drug Actemra (tocilizumab) to manage CRS. Fourteen patients experienced a respiratory or urinary tract infection, and one patient had to be hospitalized for pneumonia.
B cells reappeared after an average of 119 days, or 17 weeks, post-infusion. "What is crucial is that despite those B cells reoccurring, we don't see a flare in the disease," Mueller said.
While Miltenyi Biotec manufactured the CAR T cells for this trial, its sister drug development firm Miltenyi Biomedicine is exploring the activity of MB-CART19.1 in patients with various relapsed or refractory CD19-positive B-cell malignancies in a Phase I/II trial. The firm is also sponsoring a Phase II trial of the cell therapy in refractory patients with diffuse large B-cell lymphoma.
At the press conference, Aaron Gerds, an associate professor at Cleveland Clinic's Taussig Cancer Institute, said he expects to see CAR T-cell therapy continue to revolutionize fields outside of oncology. "That's really only scratching the surface of what CAR T cells can do," he said. "It's wonderful to see this branching out into other areas."