CAR-T trial deaths do not deter lupus patients hoping for a cure

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.

“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 agonising 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. 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. In June 2024, Kopittke went to UNC-Chapel Hill for a trial testing CAR-T, a personalised 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.” 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. 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.”