A patient with highly active relapsing multiple sclerosis died of septic pneumonia 44 days after an infusion of zolacabtagene autoleucel, or zola-cel, Bristol Myers Squibb’s autologous CD19 directed CAR-T therapy, the company disclosed on October 23 alongside interim results from the Phase 1 Breakfree-2 study at the MSToronto 2026 meeting. After the infusion the patient developed late onset motor symptoms that were not immune effector cell associated neurotoxicity syndrome, did not respond to intermittent corticosteroids and intravenous immunoglobulin, and was then treated with high dose cyclophosphamide to ablate the CAR-T cells. The patient developed septic pneumonia and died the following day. A company spokesperson told Reuters the patient had a late onset side effect, a series of other complications and was heavily pretreated before CAR-T, confounding the ability to determine the root cause, and said the death was unrelated to the program’s enrollment pause.
The wider safety picture in the 66 patient multiple sclerosis cohorts was more conventional. Cytokine release syndrome occurred in 42.4 percent of patients, 36.4 percent grade 1 and 6.1 percent grade 2, resolving in a median of two days, and neurotoxicity meeting the ICANS definition occurred in 7.6 percent, including one life threatening event that resolved within four days on corticosteroids and anakinra. Bristol Myers said there have been no other grade 5 events across its zola-cel autoimmune programs, which have treated 190 patients in Phase 1 studies, and that most patients at the higher dose level remained off disease modifying therapies, the immune reset effect the program is built on.
Context matters here. Bristol Myers voluntarily paused zola-cel enrollment in September to review safety data, after Novartis halted trials of a similar therapy following fatal events, and the company said it is working with the Food and Drug Administration to restart all studies, aiming to resume enrollment in early 2027. William Blair analyst Matt Phipps wrote that the disclosure adds to the safety overhang around rapidly manufactured cellular medicines, in BioPharma Dive’s summary.
The scientific promise of CAR-T in autoimmune disease is a one time treatment that resets the immune system. The commercial problem is that multiple sclerosis and lupus patients live with their diseases for decades on existing drugs, so tolerance for fatal treatment risk is far lower than in end stage cancer, where CAR-T was proven. Each event like this one reprices that trade off for the whole class.