She signed up for a complex clinical trial that could cure her lupus.

Sierra Butler, a West Virginia teacher, spent years of her life dealing with symptoms she couldn’t identify, including fatigue, joint pain and weight loss. In 2020, she lost more than 100 pounds and the ability to walk.

Finally, she received a diagnosis: lupusa chronic autoimmune disease that causes pain and inflammation in the body.

In some people, lupus can affect the heart and cardiovascular system. That’s what happened to Butler: During the summer of 2020, she was hospitalized multiple times, sometimes spending days in the intensive care unit. One night, she had an overwhelming sense of impending doom and called 911.

While hospitalized, she was tested for C-reactive protein, a blood marker that indicates inflammation. A healthy person will have a CRP level of 0.2 or 0.3. Butler’s level was over 100, and she was immediately admitted to the cardiac intensive care unit she had left a few days earlier.

Butler was then flown to another hospital in the state. During the flight, she suffered cardiac tamponade, a condition that prevents the heart from beating properly. Emergency surgery saved her life, but she and her medical team had to reevaluate how they treated her lupus, which was resistant to standard treatment options.

“My cardiologist called me and apologized if it was a bit of a stretch, but he asked for my permission to refer me to the Cleveland Clinic,” the 27-year-old said. “He told me he hated to see a young person with a healthy heart suffer heart problems because my lupus was not controlled. … He was concerned that if I didn’t get my lupus under control soon, I would develop very serious and irreversible heart problems.”

Butler began seeing doctors at the Cleveland Clinic in 2021. She went from balding and wheelchair-bound with limited mobility to being able to walk and drive while doctors developed a medication regimen that worked for her. She and her husband even welcomed their first child in November. In January, she had a new opportunity: She could be one of only two people in a complex clinical trial that would use CAR-T therapy to treat treatment-resistant lupus.

What is CAR-T therapy and how can it treat lupus?

CAR-T therapy, or chimeric antigen receptor T-cell therapy, essentially involves removing a patient’s white blood cells and genetically modifying them to recognize and attack problematic cells. It’s most commonly used to treat cancer, according to Dr. Emily Littlejohn, a Butler rheumatologist at the Cleveland Clinic.

The first study of CAR-T therapy as a treatment for lupus was published in 2021. Five people who had not received other lupus treatments received the therapy, which essentially uses “the patient’s own cells to find lupus in the body and kill the cells that are causing lupus activity,” Littlejohn said. The patients did “very well” and remained in remission, Littlejohn said.

“Their lupus completely disappeared. Their arthritis, their fatigue and all these other manifestations were virtually gone and they were able to get off all their medications,” Littlejohn said. “And that’s pretty amazing because lupus is a disease where you never stop taking medications. That’s really unheard of in this field.”

To treat lupus, T cells are genetically engineered to attack the overactive B cells that create inflammation in the patient’s body, said Dr. Anca Askanase, director of Columbia University’s Lupus Center, who was not involved in the Cleveland Clinic trial or Butler’s treatment. Askanase said that with CAR T therapy, the problematic B cells are “completely destroyed” by the genetically engineered cells, allowing the patient to go into remission.

A complex clinical trial

Butler and her husband had heard about CAR-T treatments for lupus being tested overseas since 2020, but had never been optimistic about her being able to try them. When Littlejohn asked her if she would be interested in participating in the Cleveland Clinic trial, she struggled to contain her emotions.

“My husband and I were in the parking lot sobbing because we were told it could be decades before this happened.
“I’m in the United States,” Butler said. “From there, we started working in the field and I’ve never regretted it. Since that phone call, my whole life has been centered around the trial.”

That marked the beginning of a complicated, months-long process that began with what Butler called “the biggest blood test I’ve ever had in my life” to make sure she met the trial’s requirements. In April, she stopped her medications and underwent leukapheresis, in which white blood cells were removed. The white blood cells were then sent to a lab and trained to attack Butler’s B cells. A week later, the clinic confirmed that the step had been successful. With that confirmed, Butler and her family moved to be near the Cleveland Clinic for the next steps of the trial.

In May, Butler began chemotherapy to “wipe out the immune system” to eliminate as many existing B cells and white blood cells as possible before the modified cells were reintroduced into his body.

Butler stayed in the hospital for two weeks to allow her immune system to recover and to monitor for side effects. Once she was released, she returned to the clinic several times a week for blood work and other tests to confirm the process had worked.

On June 3, 28 days after the cell transplant, Butler underwent another round of blood tests to confirm that the treatment was continuing to control her lupus. She was also tested to see if Butler had any physical symptoms, such as joint swelling or skin rashes. Littlejohn said that just a month after starting treatment, Butler was “doing well.”

“Her blood work is excellent. Her lupus seems much better controlled,” Littlejohn said. “We expect that to continue to improve. It’s still a little early to see the full results of the CAR-T treatment, but we expect things to continue to improve. She feels better. She has less joint pain, less rashes, less mouth ulcers and canker sores, but also serologically, in her blood, there will be less lupus activity.”

The Future of CAR-T Therapy for Lupus Treatment

Since the German study was published, interest in treating lupus with CAR-T therapy has exploded, Askanese said. Thirty-nine patients worldwide have participated in clinical trials, she said. The first U.S. trial in children with lupus was recently approved by the Food and Drug Administration.

While the results of trials around the world are promising, both Littlejohn and Askanase said there is still much work to be done before CAR-T therapy is more widely used to treat lupus. Patients in the German clinical trial are still being studied to see if and when lupus returns in their bodies, Littlejohn said. The Cleveland Clinic trial is still in its first phase of three and is only being offered to patients who have not responded to other lupus drugs, Littlejohn said.

“It’s a very promising therapy. It’s really exciting, but we still have a lot to learn about it before we can offer it to a general lupus population,” Littlejohn said.

Butler will continue to have regular appointments over the next few years. Since her last appointment on July 8, her symptoms and activity markers have continued to improve. Butler said she hopes to eventually be in remission.

“This is not just a new drug that might help manage symptoms. If the trial does for me what it has done for everyone who has received it so far, that means remission for the first time,” Butler said.