West Virginia teacher Sierra Butler had suffered for years from symptoms she couldn’t understand: fatigue, joint pain, and weight loss. In 2020, she lost more than 100 pounds and could no longer walk.
Finally, she received a diagnosis. LupusIt is a chronic autoimmune disease that causes pain and inflammation in the body.
For some people, lupus can affect the heart and cardiovascular system. That was certainly the case for Butler. Over the summer of 2020, she was in and out of the hospital, including days in intensive care. One night, a sense of impending doom hit her and she called 911.
While in the hospital, she was tested for C-reactive protein, a blood marker that indicates inflammation. A healthy person’s CRP level is 0.2 or 0.3. Butler’s level was over 100, so she was immediately admitted to the cardiac intensive care unit, from which she had been discharged only a few days earlier.
Butler was then flown by helicopter to another hospital in the state. During the flight, she suffered cardiac tamponade (a condition in which the heart cannot beat normally). Emergency surgery saved her life, but it forced her and her medical team to rethink how they treated her lupus, which was resistant to standard treatments.
“My cardiologist called and apologized for going too far, but asked permission to refer me to the Cleveland Clinic,” said the 27-year-old. “He said he would hate to see a young person with a healthy heart develop heart problems because my lupus was not controlled. … He was afraid that if my lupus was not controlled quickly, I would develop very serious and irreversible heart problems.”
Sierra Butler
Butler began seeing doctors at Cleveland Clinic in 2021. Bald and wheelchair-bound, her mobility was limited, but doctors perfected a medication regimen that helped her walk and drive again. She and her husband welcomed their first child in November. In January, a new opportunity presented itself: She could be one of just two people to participate in a complex clinical trial to treat treatment-resistant lupus with CAR-T therapy.
What is CAR-T therapy and how does it treat lupus?
CAR-T therapy, or chimeric antigen receptor T-cell therapy, essentially removes a patient’s white blood cells and genetically engineers them to recognize and attack problematic cells. It’s the type of therapy most commonly used to treat cancer, says Emily Littlejohn, M.D., a rheumatologist at Butler MD at the Cleveland Clinic.
The first study to investigate CAR-T therapy as a treatment for lupus Published in 2021Five people have been treated with the treatment after other lupus treatments had failed, Littlejohn said. The treatment essentially uses the patient’s own “cells to find lupus in the body and kill the cells that are causing the lupus activity.” Littlejohn said the patients are doing “very well” and remain in remission.
“Their lupus has completely disappeared. Their arthritis, fatigue, and other symptoms have basically disappeared, and they’ve been able to get off all of their medications,” Littlejohn says. “This is so amazing because lupus is a disease where you don’t have to stop taking your medication. It’s unheard of in this field.”
To treat lupus, T cells are engineered to attack overactive B cells that cause inflammation in patients’ bodies, said Dr. Anka Askanadze, director of the Lupus Center at Columbia University, who was not involved in the Cleveland Clinic trial or Butler’s treatment. In CAR-T therapy, the engineered cells “totally destroy” the problematic B cells, putting patients in remission, Askanadze said.
Complex Clinical Trials
Butler and her husband had been reading about CAR-T treatments being tested for lupus overseas since 2020, but were never optimistic about whether they would be able to try it. When Littlejohn asked her if she would be interested in taking part in the Cleveland Clinic trial, she couldn’t contain her emotions.
“My husband and I were just crying in the parking lot because we were told this could take decades to happen.
“I was in America,” Butler said, “and from there we hit the ground running and I never looked back. Since that phone call my whole life has revolved around the trial.”
From there, a complicated, months-long process began, starting with what Butler called “the most blood tests I’ve ever had in my life” to make sure she met the trial’s requirements. In April, she stopped taking her medication and underwent leukapheresis, a procedure to remove her white blood cells. The cells were then sent to a lab where they were trained to attack Butler’s B cells. A week later, the clinic confirmed that this step was successful. With that confirmed, Butler and her family moved closer to the Cleveland Clinic for the next steps in the trial.
Annie O’Neill, Cleveland Clinic
In May, Butler began chemotherapy to “wipe out her immune system” by removing as many of her existing B cells and white blood cells as possible, before the modified cells were returned to her body.
Butler remained in the hospital for two weeks to allow her immune system to recover and to be monitored for possible side effects. After she was released, she returned to the clinic multiple times a week for blood and other tests to see if the treatment was working.
On June 3, 28 days after the cell transplant, Butler had another blood test to ensure the treatment was keeping her lupus in check. Tests were also done to see if Butler had any physical symptoms, such as swollen joints or a rash. Dr. Littlejohn said Butler was “doing well” just one month into treatment.
“Her blood work is good. Her lupus appears to be much better controlled,” Dr. Littlejohn said. “We’re hopeful that she’ll continue to get better. It’s still a while before we know the full results of the CAR-T treatment, but we expect that her condition will continue to improve. She’s doing better. She has less joint pain, less rash, less canker sores and stomatitis, and serologically there is less lupus activity in her blood.”
Annie O’Neill, Cleveland Clinic
The future of CAR-T therapy in treating lupus
Since the German study was published, there has been an explosion of interest in treating lupus with CAR-T therapy, Ascanese said. Thirty-nine patients worldwide have enrolled in clinical trials, she said. The first U.S. trial in children with lupus was recently conducted. Food and Drug Administration Approval.
While results from clinical trials around the world have been promising, both Littlejohn and Ascanase said there’s still a long way to go before CAR-T therapy is more widely used to treat lupus. Littlejohn said patients in the German trial are still being studied to see if and when lupus will return in their bodies. The Cleveland Clinic trial is still in the first of three phases, and is only open to patients for whom other lupus medications have failed, Littlejohn said.
“This is a very promising treatment. It’s really exciting, but there’s still a lot to learn before we can offer it to the general population of lupus patients,” Littlejohn said.
Butler will continue to have regular check-ups over the next few years. As of her most recent appointment on July 8, her symptoms and activity markers continued to improve. Butler said she is hopeful that she will eventually go into remission.
“This isn’t just a new drug that might help ease symptoms. If this trial works for me the same way it has worked for everyone who has tried it before, it will mean my first remission,” Butler said. “I’ve never been in remission before, so this will be life-changing.”
