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A phase I trial of zolacabtagene autoleucel (zola-cel), a CAR-T therapy targeting MS, reported one patient death from septic pneumonia 44 days after treatment. Despite the setback, most participants showed encouraging results, with all 60 patients at the higher dose level remaining off disease-modifying therapies at last follow-up. Researchers caution that the field is still learning the nuances of CAR-T in autoimmune disease.
A phase I trial called Breakfree-2 is testing zolacabtagene autoleucel (zola-cel), a CD19-directed CAR-T cell therapy, in patients with highly active relapsing and progressive multiple sclerosis (MS). The therapy aims to produce an "immune reset" by deeply depleting autoreactive B cells — a key driver of MS — and allowing immune reconstitution. Results presented at MSToronto2026 showed encouraging efficacy signals, but the trial was also marked by a patient death.
One participant with highly active relapsing MS developed extrapyramidal motor symptoms on day 17 post-infusion. After receiving high-dose cyclophosphamide on day 41 to target circulating CAR-T cells, the patient developed septic pneumonia and died on day 44. The cause is still under investigation and was not related to immune effector cell-associated neurotoxicity syndrome (ICANS). Developer Bristol Myers Squibb had already paused the zola-cel program in September to evaluate safety findings.
Key Takeaways:
Why it matters: CAR-T therapy is an emerging frontier for autoimmune diseases like MS, but safety remains a critical concern. This death — alongside three fatalities in a separate Novartis CAR-T autoimmune trial — underscores the need for careful patient monitoring and further research before broader use.
