Why Lupus Patients Still Seek CAR-T Trials Amid Safety Concerns and Deaths
By Julie Steenhuysen
Lupus Patients Weigh Risks and Hope in Experimental CAR-T Therapies
CHICAGO, Nov 11 (Reuters) - Lupus patients struggling with the debilitating disease are lining up to try experimental CAR-T therapies even after the recent deaths of four patients in clinical trials for a variety of autoimmune diseases, according to doctors who treat the life-threatening condition.
The trials remain halted and full details of the deaths — three linked to Novartis and one to Bristol Myers Squibb — have not been released.
Still, patients are willing to take the risk, compelled by accounts of people with advanced disease who were able to stop all medications and reclaim normal lives.
Patient Demand Despite Setbacks
"I have patients that are literally waiting to get in," said Dr. Anca Askanase, chief of rheumatology at the Hospital for Special Surgery in New York, who has enrolled patients in the Bristol Myers CAR-T trials.
Systemic lupus erythematosus, or SLE, the most common and severe form of lupus, causes agonizing joint pain and raises the risk of stroke, heart attack and kidney disease. Current treatments, which range from steroids to immunosuppressants and targeted biologics, often fail to control the disease. Some 10% to 15% of people with lupus die prematurely.
A Patient’s Journey: Brittan Kopittke
Brittan Kopittke, 27, who works for the University of North Carolina helping to counsel patients considering CAR-T, was diagnosed with lupus at age 22. SLE, which affects about 300,000 people in the US, typically develops between the ages of 15 and 44.
What began as a rash on her chest rapidly progressed to crippling joint pain, mouth sores and crushing fatigue. Steroids to reduce inflammation and the antimalarial drug hydroxychloroquine to tamp down antibodies attacking her healthy cells and tissues failed.
"My mouth sores were rampant. I was struggling to eat. I was struggling to drink. I was just very, very miserable," she said.
Despite trying a cocktail of medicines, her disease advanced, attacking her kidneys, heart and lungs.
"I had reached the end of the line with treatments,” she said.
Undergoing CAR-T Therapy
In June 2024, Kopittke went to UNC-Chapel Hill for a trial testing CAR-T, a personalized immunotherapy successfully used to treat blood cancers. It involves removing blood cells called T cells, genetically reengineering them to attack rogue immune cells, and reinfusing them with the aim of growing new, healthy immune cells.
Kopittke developed two dangerous reactions: cytokine release syndrome, which causes systemic inflammation, and a life-threatening, high-grade neurological complication called ICANS that left her unresponsive for three days.
Now, some two years into remission, Kopittke said she does not “sugarcoat” the risks when advising patients. "But I do say that I would do this again."
Clinical Trials and Industry Response
150 Trials Underway
Novartis, Bristol Myers, and other companies with approved CAR-T cancer therapies, such as Johnson & Johnson and Gilead, are currently testing the technology against other hard-to-treat diseases.
There are about 150 trials underway pursuing CAR-T for lupus, as well as many others for myasthenia gravis, scleroderma, myositis, multiple sclerosis and stiff-person syndrome.
"There's billions and billions of dollars pouring into this space,” said P.J. Utz, a Stanford Medicine autoimmunity researcher.
Recent Deaths and Trial Halts
The risks became clear when Novartis in late August said it halted eight trials of its experimental rap-cel CAR-T therapy in autoimmune and neurological disorders after three patients died from a rare but known hyperinflammatory complication called IEC-HS.
Novartis, in an emailed statement, said it is working with multiple investigators and external academic experts to understand the root cause of the deaths and will share its findings "once the analysis is completed and the results can contribute to furthering patient care."
Bristol also paused enrollment in its CAR-T autoimmune trials, citing temporary inflammatory events in patients. On October 23, it announced the death of a multiple sclerosis patient in one of the trials but said it had identified the cause of the safety issue and hopes to resume testing in 2027.
Understanding the Safety Concerns
Piecing Together What Happened
The revelation of deaths in the Novartis trials surprised doctors eager to try CAR-T, buoyed by the success of Georg Schett of the University of Erlangen-Nuremberg. In 2022, Schett published a paper in the New England Journal of Medicine showing five lupus patients achieved remission with CAR-T. Subsequent studies showed lasting remission.
The Novartis deaths have left doctors in the dark, Schett said. The company needs to disclose what diseases the patients had, how well controlled their diseases were and what emergency treatments they received, Schett added.
Without those details, he said, doctors enrolling patients in other trials are left to speculate. "This is very sad for the community."
Schett said he and CAR-T inventor Carl June of the University of Pennsylvania have tried to piece together what happened in the Novartis trials for an article they have submitted to NEJM.
Potential Causes and Manufacturing Differences
He attributes the rare hyperinflammatory events in part to Novartis' compressed manufacturing process, which reduces the time it takes to produce the cells from more than 10 days to fewer than two.
With this process, patients receive cells in an immature form, which Schett suggests is triggering a severe inflammatory response as cells expand in patients' bodies. "We don't see that in other programs," he said.
He and others were less concerned about the more familiar side effects reported by Bristol Myers.
Managing Side Effects and Looking Ahead
"We have treated high-grade inflammatory events that have been reversible with treatment," said Kopittke's doctor, Saira Sheikh, of the University of North Carolina, who chairs a network of nearly 70 lupus clinical trial centers.
Dr. Cuoghi Edens, a rheum
