CAR T therapy for autoimmune disease exploded in 2024. Here’s what you may have missed

After first generating excitement in late 2022, this year was a bonanza for news about chimeric antigen receptor T-cell therapies for autoimmune rheumatic diseases.

The process — in which the T cells of patients or donors are re-engineered to eliminate pathological immune cells, effectively producing a deep reset of the immune system — appears to offer something previously unthinkable for patients with lupus and other autoimmune diseases: long-term remission, if not a cure.

Originally applied in cancer, CAR T-cell approaches are now being investigated in Sjögren’s disease, systemic sclerosis, rheumatoid arthritis and numerous other diseases in the rheumatology arena.

Still, there is much to learn. Relapse remains possible, and there are open questions about which patients are the best candidates for this therapy. It was a hopeful year for CAR T, but also one that produced hard questions.

Keep reading for a look back at this year’s coverage.

CAR T-cell therapy brings sustained, drug-free remission in three autoimmune diseases

Single injections of CD19 chimeric antigen receptor T-cell therapy brought long-lasting remission to 15 patients with three different autoimmune diseases, according to data published in The New England Journal of Medicine.

“Although antibody-based B-cell targeting certainly improved treatment of autoimmune disease, achieving long-lasting drug-free remission has proven elusive,” Fabian Müller, MD, of the University of Erlangen-Nuremberg, in Germany, and colleagues wrote. “CAR T cells could potentially achieve this goal by deep depletion of B cells through the targeting of the surface molecule CD19, which is expressed on a wide spectrum of B cells and plasmablasts.” Read more.

CAR T-cell therapy may be a ‘miracle,’ but it is too soon to say ‘cure’

It has been at least 2 years since the first cohort of patients with lupus underwent chimeric antigen receptor T-cell treatment, and, at least so far, for every one of them, each new dawn represents another day spent in full remission.

“All five SLE patients are in remission and drug-free,” Georg Schett, MD, of Friedrich-Alexander University, in Germany, whose lab produced the landmark 2022 study in Nature Medicine, told Healio Rheumatology. “All of them are now 2 years disease-free, and the first of them is now 3 years disease free.” Read more.

CAR T cells 1 year later: What have we learned?

Nearly 1 year ago, I wrote my first editorial about the emergence and excitement surrounding the early experience with CAR T cells — CAR T Cells in Autoimmunity: A Potential Therapy About to Explode.

That excitement had been driven by the pioneering work of Georg Schett, MD, which at that time was based on the experience of a single patient with refractory lupus put in deep, drug-free remission through the administration of an autologous CD19-targeting T-cell therapy. The buzz surrounding this carefully studied single patient was indeed explosive, yet naturally left many unanswered questions. Read more.

CAR T-cell therapy remains the ‘hottest story’ in lupus, autoimmune disease

Positive results for chimeric antigen receptor T-cell therapy in systemic sclerosis and myositis have added fuel to the fire of recent landmark data in lupus, said a speaker at the Congress of Clinical Rheumatology East.

“The hottest story in lupus and perhaps in autoimmune diseases in general are CAR T cells,” Ronald van Vollenhoven, MD, PhD, chair of the department of rheumatology and clinical immunology at the Amsterdam Medical Center, and director of the Amsterdam Rheumatology Center Academic Medical Center, told attendees. “It is an extremely complex treatment from a technical point of view.” Read more.

Patient with lupus treated with KYV-101 CAR T-cell therapy relapses after 5 months

A patient with lupus nephritis treated with KYV-101, a chimeric antigen receptor T-cell immunotherapy, saw their disease return 5 months after initially showing a response to the treatment, according to the manufacturer.

The patient, who had a “high BMI,” was treated with a half-dose of 50 million cells, James Chung, MD, PhD, chief medical officer at Kyverna, said during a press conference at the EULAR 2024 Congress. Read more.

FDA grants orphan drug designation to CAR T-cell therapy for systemic sclerosis

The FDA has granted orphan drug designation to Cabaletta Bio’s CAR T-cell investigational therapy for the treatment of systemic sclerosis, according to a press release from the manufacturer.

The drug, currently known as CABA-201, is a 4-1BB-containing, fully human CD19-CAR T cell, Cabaletta said in the release. According to the company, a clinical trial program including four phase 1/2 studies is advancing to examine CABA-201 across multiple autoimmune diseases, including SSc. Read more.

FDA clears new drug application for CAR T-cell therapy in SLE with lupus nephritis

The FDA in February cleared an investigational new drug application for an allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for the treatment of systemic lupus erythematosus with lupus nephritis, according to the manufacturer.

The therapy, developed by Atara Biotherapeutics and currently known as ATA3219, is based on the company’s novel allogeneic Epstein-Barr virus T-cell platform and targets CD19+ relapsed or refractory B-cell malignancies. An investigational new drug application for ATA3219 was previously cleared in non-Hodgkin’s lymphoma, according to a press release from Atara. Read more.

FDA authorizes first CAR T-cell trial for children with lupus

In April, the FDA authorized the first chimeric antigen receptor T-cell clinical trial for children with systemic lupus erythematosus.

The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will be led out of Seattle Children’s and is expected to launch this summer, according to a blog post from the hospital. Read more.

Severe disease, strict endpoints in CAR T trials ‘could be a way through the regulators’

Regulatory trials of chimeric antigen receptor T-cell therapies for autoimmune diseases could be successful with a focus on patients with severe disease and strict endpoints, according to a speaker.

After reviewing his team’s recent successes in using CAR T-cell therapies for autoimmune diseases at the 2024 Congress of Clinical Rheumatology West, Georg Schett, MD, vice president of research and head of internal medicine at Friedrich-Alexander University Erlangen-Nürnberg, in Germany, was asked for his views on potential regulatory paths forward. Read more.