A cutting-edge cancer therapy offers hope for patients with lupus

Boston Globe

23-06-2025

By fall of 2024, Le had run out of conventional treatment options. That's when Dr. Meghan Sise, her physician, offered her a chance to participate in a clinical trial that was testing a new therapy, borrowed from the field of cancer research.
'Let's try it,' Le told Sise, who is a principal investigator on the trial. 'I have nothing to lose.'
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CAR T-cell therapy, a kind of 'living drug' that modifies patients' immune cells to help them attack misbehaving ones, has been used with significant success to treat some cancers, particularly of the blood. A growing body of evidence has suggested that the therapy can also treat a severe form of lupus that, at best, can be managed as a lifelong condition and, at worst, resists treatment and can lead to organ failure and death.
'It's really promising, and honestly the first therapy that we've talked about as a cure,' said Dr. Lisa Sammaritano, a rheumatologist at the Hospital for Special Surgery — Weill Cornell Medicine and the lead author on a set of recently updated guidelines for lupus treatment. Until now, she said, 'we haven't had a cure — we've had control.'
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Whether this is truly a cure, and for whom, remains to be seen. Clinical trials for patients with severe disease are still in early phases, and CAR T-cell therapy, which must be personalized to each patient, is extraordinarily expensive.
'I'm hoping that it is a common future therapy,' Sammaritano said, 'but we're not at the point yet where we can say that with confidence.'
Lupus, or systemic lupus erythematosus, is an autoimmune condition in which the body develops antibodies against its own DNA and other cellular material. The name derives from the Latin for 'wolf' because the skin lesions the disease sometimes causes were once thought to resemble wolf bites, some say.
The disease can cause joint pain, rashes, severe fatigue and inflammation in organs, said Dr. April Barnado, a rheumatologist and assistant professor of medicine at Vanderbilt University Medical Center. Typically, symptoms first appear between ages 15 and 44. Of the estimated 3 million people with lupus worldwide, 90 percent are women.
Lupus often strikes 'at a time when women are raising families, or they're caregiving, or they're trying to get promoted at work,' Barnado said. 'They wake up and feel like they have the flu or a viral infection a few days a week every week. That's pretty debilitating.'
A patient's symptoms can flare up in response to a trigger like stress or an infection. Le, for example, would wind up in the emergency room every few months with a severe rash, joint swelling, and pain and sores in her mouth. She would pass out for hours from exhaustion.
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'It would take me two months to get healed back to normal,' Le said. She frequently had to take medical leave from her job.
Le is among the roughly 50 percent of lupus patients who have inflammation in their kidneys, a condition known as lupus nephritis. Between 10 percent and 30 percent of these patients will eventually need dialysis or a kidney transplant, said Sise, the director of onconephrology at Massachusetts General Hospital.
Treatment usually involves steroids and immunosuppressive drugs. Steroids tamp down inflammation, but they carry major risks with long-term use, including cardiovascular disease and osteoporosis. 'Nothing can bring the symptoms under control more quickly,' Sammaritano said, 'but the longer you stay on it, the more the side effects.'
Newer drugs that target specific parts of the immune system are less harmful, but patients often require treatment for decades, and many still won't be able to get their disease under control.
With the rise of CAR T-cell therapy in oncology, Dr. Georg Schett, a rheumatologist and immunologist at the University of Erlangen in Germany, started mulling a new idea to help lupus patients.
Lupus causes the body's B cells — white blood cells that produce antibodies — to go haywire. In CAR T-cell therapy, a patient's own T cells, a type of immune cell, are extracted and engineered to wipe out disease-causing B cells. They're then put back in the body, where they replicate, acting like 'serial killers' that can clear out B cells even from deep within tissues that other drugs can't reach, Schett said.
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Perhaps most tantalizing to Schett was the idea that a single infusion might do the trick, freeing young women from the constraints, and uncertainty, of living with lupus.
'The disease dominates their life,' he said.
Janina Paech, a medical student in Cologne, Germany, was among the first to receive the treatment. Paech was diagnosed with lupus in 2015, at age 16. She developed a severe rash anytime she went out in the sun. Her joints ached. Her hair fell out. And she was so fatigued that she slept most of the day and night.
With steroids and immunosuppressive drugs, Paech went into remission. But she had high blood pressure, more hair loss and so much swelling it gave her a 'moon face' — all side effects of the medications. Her thinned skin caused extreme sensitivity and pain.
Despite treatment, Paech had flare-ups of lupus amid the stress of medical school. Eventually, her kidneys and other organs started to fail. Paech's father reached out to Schett, whom he had read about in a newspaper.
Paech received the CAR T cells in 2021, and within days, her symptoms retreated. They still haven't returned.
Since then, dozens of patients worldwide have been treated with the therapy, which has not yet been approved for lupus by the Food and Drug Administration.
The therapy has risks, including the possibility of systemic inflammation that can cause high fever and, rarely, neurological symptoms.
Dr. Carl June, a professor of immunotherapy at the University of Pennsylvania and a pioneer of CAR T-cell therapy, said that its potential for treating lupus and other autoimmune diseases was apparent to him early on. But it was the technology's use in cancer treatment that really 'paved the way' to start testing it in other conditions, he said.
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The treatment is still prohibitively expensive, with one-time costs for approved cancer therapies approaching $500,000 or more.
And researchers don't yet know how patients will fare in the long run. 'The big question is: How long does it last? Are they cured?' June said. A recent large trial of CAR T-cell therapy for multiple myeloma found that one-third of patients remained in remission five years after therapy, though other studies have shown median survival times after treatment ranging from a few months to a couple of years.
Of the two dozen lupus patients Schett has treated, all but one went into remission and remained off treatment after at least six months, and some for longer than four years. (One patient who had a relapse underwent CAR T-cell therapy a second time and is now symptom-free.)
It will be years before doctors know for sure whether those results can last. In the meantime, patients say the treatment has given them an opportunity to live a normal life.
'I get to be more careless,' Paech said. 'That was something that was very hard for me to learn because I didn't learn it as a young adult.'
Before the treatment, she couldn't travel for fear of getting sick and needing to carry medications around. But Paech has now been able to visit Egypt, South Africa and Australia. Even when her lupus was controlled with steroids, she said, she felt well enough to do only one activity a day. 'I could go to the mall and that was it — I couldn't do anything else,' she recalled. 'Now going to the mall is like one out of 10 things in the day.'
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Le has been able to return to her job at a factory and can now get a good night's sleep before waking up to start work at 5 a.m. (She used to wake several times a night to urinate because of her kidney disease.) Pain-free and more energetic, she can now take long walks and lift heavy grocery bags. She also hopes to try to conceive later this year.
Before her treatment, Le often answered 'yes' to many of the symptoms on Sise's checklist, a reflection of how debilitating her condition had become. But on her recent visit in May, six months after she received CAR T-cell therapy, she answered 'no' to every question.
This article originally appeared in
.