Autoimmune patients in CAR-T study see striking improvements across lupus and other diseases

Autoimmune patients in CAR-T study see striking improvements across lupus and other diseases
Lei Lei Wu
News Reporter
SAN DIEGO — All of the first 15 autoimmune disease patients who received CAR-T therapy at a German hospital saw the debilitating symptoms of their diseases, including lupus and myositis, substantially improve or go away entirely, according to new research results shared Saturday.

In 2021, a team of researchers from the University Hospital Erlangen began the first study of CAR-T therapy in patients with autoimmune diseases, making waves across the field when they announced that the first five patients with lupus all went into remission.

Fabian Müller
That number has now increased to eight lupus patients whose disease cleared, study investigator Fabian Müller reported at the American Society of Hematology annual meeting. Müller shared during his presentation a photo of a patient with lupus who had rashes associated with the disease all over their back. But after treatment, their skin was completely cleared.

“The results were very impressive,” Larry Kwak of City of Hope’s cancer center, who was not involved in the research, told Endpoints News following the presentation.
The university hospital also gave a single infusion of CAR-T cells to people with other autoimmune disorders, including idiopathic inflammatory myositis, where the muscles become inflamed, and systemic sclerosis, which causes the body to produce too much collagen.

All three patients with myositis also went into remission after three months. And of the four sclerosis patients, the three that have been on the study for over three months also have seen the activity of their disease go down substantially.

While the patients had to receive chemotherapy to clear space for the engineered cells, after the CAR-T treatment all 15 patients were able to stop taking the immunosuppressive drugs that are meant to keep their diseases at bay.

The fact that all 15 patients have responded to CAR-T treatment and have not had their disease return is notable, since in blood cancers where similar cell therapies are currently approved, more than half of patients may relapse or not respond. Notably, the patients also had milder side effects than those who’ve received CAR-T therapy for cancer. Eleven patients experienced low-grade cytokine release syndrome, an immune response to the therapy, and one patient experienced grade 1 neurotoxicity related to immunotherapy treatment in the form of vertigo.

The immune cells in autoimmune disease patients treated with CAR-T therapy appear to behave differently from those with cancer, and more research needs to be done to understand how the therapy works, Müller said.

Patient number one
A surge of advancements in oncology and immunology is opening up new pathways in the field, as medical researchers look for new ways to attack both types of diseases, and where there might be crossovers between them.

The German researchers, for example, had seen a mouse study conducted by University of Tennessee researchers that suggested using cell therapies for autoimmune diseases could work. They had an experimental CAR-T therapy developed by Miltenyi Biomedicine with which they had treated some cancer patients. And they had a patient with lupus who was running out of options and time.

“We did not know what to expect to start with patient number one,” Müller told Endpoints. “Nobody really knew what was going to happen.”

Now, the patient has been in remission for over two years and is in school.

“When I met her in February, she was in her midterm examinations,” Müller said. “Three years ago, she would have never thought she’s ever going to go back to something like that.”

So far, the researchers have treated 16 patients through a compassionate use program, with another patient expected to receive treatment in January. Müller said that these patients would typically be too sick to qualify for clinical trials, and that the university hospital also has a separate basket study ongoing where it expects to treat 25 autoimmune disease patients.

A new arena for immunotherapy
The German team’s research has ignited the interest of the biopharma industry. Several companies are now making their own strides into autoimmune cell therapy.

Frank Neumann
Bristol Myers Squibb and Novartis both have started CAR-T studies in lupus. Bristol Myers also recently received FDA clearance for a study in multiple sclerosis, chief medical officer Samit Hirawat said. Gilead’s cell therapy subsidiary Kite also plans to start research in autoimmune diseases, Kite’s head of clinical development Frank Neumann told Endpoints Saturday, though he declined to outline specific plans.

A slate of biotech companies is exploring the possibility as well, including Kyverna Therapeutics, Cabaletta Bio and Cartesian.

Then there’s the possibility that other therapies developed for cancers, such as bispecific antibodies and “off-the-shelf” CAR-T therapies, could be useful for treating autoimmune diseases, Müller noted. While “off-the-shelf,” or allogeneic, CAR-T therapies that use donor cells instead of a patient’s own cells have largely floundered in cancer indications, Müller theorizes that they may be enough to give the “one decent punch” to reset patients’ immune systems in autoimmune diseases.

“Before, autoimmune diseases were exclusion criteria for CAR-T,” Müller said. “Now it is actually switching, that we are more courageous and just are like, ‘Well, let’s try it. Maybe it works.’”

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Lei Lei Wu
News Reporter
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@leilei_wuu