CAR-T delivers ‘amazing’ drug-free remission in autoimmune diseases
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Chimeric antigen receptor T-cell therapy produced persistent, drug-free remission in patients with one of three different B-cell autoimmune diseases, researchers reported at ASH Annual Meeting and Exhibition.
Patients with active and progressive systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM) and systemic sclerosis (SSc) received CAR-T, and all 15 in the study halted immunosuppressive drugs due to medical improvements.
“It’s amazing,” Fabian Mueller, MD, head of CAR T-cell unit at University Hospital of Erlangen in Germany, told Healio.
“These are patients in their mid-20s, on average,” he added. “They can’t participate in a normal life. They don’t go work out. They don’t have jobs. They’re just sick. It’s really a disease that takes away your quality of life at the time when you have the best time of your life.”
Each of the patients who received the CD19-directed CAR-T has returned to living their “regular lives,” Meuller said.
CAR-Ts had been “efficient” in treating SLE in a preclinical mouse model according to a pair of published papers, he said, but treating SLE in humans with CAR-Ts came about by chance. A laboratory already had CAR-Ts made, and a patient progressing toward death decided to give the last-ditch novel therapy a try.
“Life threatening,” Mueller explained. “The heart failed, the lungs failed, the kidneys failed, and in that situation, where no other treatment did the job any longer, we gave the CARs, and within 30 days the entire disease was gone.”
In the study, eight patients had SLE, four had SSc and three had IIM. They had a median age of 36 years, disease duration of 4 years and a median of five failed treatments.
All patients with SLE achieved complete remission within 3 months, all patients with IIM had significant improvement and serum CK levels normalized, and three patients with SSc had reduction in disease activity.
Adverse effects included cytokine release syndrome (grade 0 in four patients, grade 1 in 10, grade 2 in one) and one case of grade 1 immune effector cell-associated neurotoxicity syndrome. No patients experienced bone marrow suppression.
“We’re used to very severe side effects of these CARs,” Mueller said.
“They’re really life threatening in certain situations where the CARs are putting up so much inflammation, and it’s truly amazing that in these patients [with autoimmune disease], the side effects are substantially less,” he added. “Most of them never have severe side effects — some of them actually have no side effects at all.”
He also mentioned increased inflammation and respiratory and urinary tract infections due to immunosuppression, but that the adverse effects are well worth the benefits.
“Myositis patient No. 1 was working in construction and then he lost his job — he just couldn’t do the work anymore,” Mueller said. “He was 42 at the time, and he was walking like a very elderly patient.
There were no treatment options left for the patients, Meuller recalled.
“I remember at about month 3 when he came in, he had extremely strong pain in his foot,” he added. “ It just hurt him because the muscles gained so much strength that the bones couldn’t keep up with the new force that was attacking the bone in the end. He was walking too far.”
The study results wowed clinicians at ASH.
“So cool,” Marcela V. Maus, MD, PhD, director of the cellular immunotherapy program at Mass General Cancer Center and Healio | HemOnc Today Associate Medical Editor, told Healio. “It also starts to build cell therapy as not just belonging inside cancer centers, but really this is a modality of therapy that can cut across multiple diseases.”
Nevertheless, Maus did have questions about the effect chemotherapy played in the patients’ improvement.
“[Chemotherapy] helps the CAR-T engraft, and I have no doubts about that,” Maus said.
“It makes the CAR-T work better, but chemotherapy also has effects on its own,” she added. “I think it is going to be tricky to deconvolute at least the short-term effects of chemotherapy versus chemo plus CAR-T.”
Both Maus and Mueller discussed how the study highlighted the need for collaboration between differing fields.
“People are trying CAR-T now in diseases that I don't think I’d ever heard of before,” Maus said. “I've had calls — even just in the last week — about CAR-T for multiple sclerosis, CAR-T for Alzheimer’s disease, CAR-T for some of these muscle disorders. There’s so much excitement in the field, and I think that's just wonderful.”
However, she said expansion may dictate changes to how institutions structure cellular therapy care.
“We’re going to need some centralized structures within academic medical centers to have all of that in one place for a patient who’s received cell therapy because it’s just too much to build separately for every different disease group,” Maus explained. “There’s got to be some economies of scale, like centralized cell processing and specialists who really understand the nuts and bolts of the field from the science to the clinical to the logistics and regulatory aspects that are kind of unique to cell therapy.”
For more information:
Marcela V. Maus, MD, PhD, can be reached at mvmaus@mgh.harvard.edu.
Fabian Mueller, MD, can be reached at fabian.mueller@uk-erlangen.de.
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Mueller F, et al. Abstract 220. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023; San Diego.
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