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A participant in a phase I study of the experimental CAR-T therapy zola-cel died from septic pneumonia 44 days after treatment. Investigators have not established the cause of the event, which followed high-dose cyclophosphamide; the study’s presenter said it was not related to ICANS. The findings come amid safety reviews of CAR-T treatments for autoimmune disease.
A participant in a phase I study of zola-cel, an experimental CAR-T treatment for multiple sclerosis, died from septic pneumonia 44 days after receiving the therapy, according to study findings presented at an international MS meeting. The cause of the event is still under investigation, and the study’s presenter said it was not related to ICANS, a neurological complication associated with some CAR-T treatments.
Jeffrey Cohen, MD, of the Cleveland Clinic Mellen Center, reported the death from the Breakfree-2 study at MSToronto2026, a joint meeting of the European and Americas committees for treatment and research in MS. The participant had highly active relapsing MS. The death occurred after the study’s June 2026 data cutoff, so it was not included in the data summarized at the presentation.
According to Cohen’s account, the patient developed rigidity and tremor on day 17 after the zola-cel infusion and received intermittent corticosteroids and intravenous immunoglobulin. On day 41, clinicians gave high-dose cyclophosphamide to target circulating CAR-T cells after identifying no alternative cause for the symptoms. Septic pneumonia developed on day 43, and the patient died the following day.
Cohen said the participant’s CAR-T cell expansion was in line with that of other participants. He also said the pathogenesis of the death is not fully understood and that the case remains under investigation. The report states that cyclophosphamide was part of the original treatment protocol and was administered again later in this case; it does not establish that the drug caused the infection or death.
Safety Questions After the Fatal Event
The death adds a serious safety event to early evidence on using CAR-T cells for autoimmune disease, where the approach remains experimental. The Breakfree-2 study’s primary goal was to assess safety and tolerability, while its efficacy measures were secondary. A fatal event can affect how researchers and regulators weigh risks, monitor participants and decide whether a treatment program should proceed.
The findings also matter because the developer, Bristol Myers Squibb, had paused its zola-cel program in September to evaluate safety findings. The report places the death in a broader period of scrutiny of CAR-T therapies for autoimmune conditions, but does not say that the event was caused by the same mechanism as deaths reported in another company’s trial. Cohen specifically said this death was not related to ICANS.
Possible treatment benefits in the study should be read alongside those risks and the limits of the evidence. Cohen described the results as coming from small, largely uncontrolled and open-label trials with relatively short follow-up, and said efficacy findings should be interpreted cautiously. The reported outcomes do not establish that zola-cel is effective or safe for wider use.
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Breakfree-2 Study and Earlier Safety Review
Breakfree-2 evaluated zola-cel in three groups: people with highly active relapsing MS, people with progressive MS, and people with refractory myasthenia gravis. The presentation covered the two MS groups, which together included 66 participants: 30 with highly active relapsing MS and 36 with progressive MS. The progressive group included 12 people with primary progressive MS and 24 with non-relapsing secondary progressive MS.
Participants received lymphodepletion with fludarabine and cyclophosphamide before a single zola-cel infusion. The study tested two dose levels, although the source report lists the same cell count for both, so the dose distinction is not clear from that account. The data cutoff was June 2026, and the fatal event was reported afterward.
In the data presented, 42.4% experienced cytokine release syndrome, all reported as grade 1 or 2 and resolving in a median of two days. ICANS was reported in 7.6%; most cases were grade 1 or 2. One grade 4 ICANS case in a participant with progressive MS resolved within four days after treatment with corticosteroids and anakinra. The report said no other Grade 5 events had been reported in the trial or among 190 patients treated with zola-cel in phase I autoimmune-disease studies.
In September, Bristol Myers Squibb paused its zola-cel program to evaluate safety findings. Around the same time, Novartis reported three fatal ICANS cases in autoimmune-disease trials of a different CAR-T product, rapcabtagene autoleucel. Those cases are separate from the Breakfree-2 death, which Cohen said was not related to ICANS.
“The pathogenesis of that event is not fully understood.”
— Jeffrey Cohen, MD, Cleveland Clinic Mellen Center
Cause and Treatment Decisions Remain Open
Investigators have not established why the participant developed septic pneumonia or whether the infection was connected to zola-cel, the later cyclophosphamide dose, another treatment, or other factors. Cohen said the pathogenesis was not fully understood. The available report does not provide a final investigation outcome or a detailed account of the patient’s condition before treatment.
It is also unclear what the event will mean for the paused zola-cel program, including whether the company or study investigators will change protocols, enrollment or monitoring. The source does not report a regulator’s decision or say whether the study was halted. The available safety and efficacy figures are based on the presentation’s June cutoff and should not be treated as a complete account of later follow-up.
Investigation and Program Review
The immediate next development is the outcome of the investigation into the fatal septic pneumonia event. Further information from the investigators or Bristol Myers Squibb may clarify the circumstances, any suspected contributing factors and whether study procedures will change. The company’s previously announced safety review will also determine the status of the zola-cel program.
Readers should look for updated study data and official statements rather than assume that this single report establishes a cause or a final decision about the therapy. Any further clinical results will need to be considered alongside the study’s size, follow-up period and safety record.
Key Questions
What happened to the participant in the zola-cel study?
The participant developed motor symptoms after treatment, later developed septic pneumonia and died on day 44 after the zola-cel infusion, according to the study report.
Has the cause of death been determined?
No. Jeffrey Cohen said the event’s pathogenesis is not fully understood and remains under investigation. The report does not establish that zola-cel or cyclophosphamide caused the death.
Was the death attributed to ICANS?
No. Cohen said the death was not related to ICANS. The patient’s reported symptoms included rigidity and tremor, followed later by septic pneumonia.
How many people were included in the MS groups?
The presentation covered 66 people with MS: 30 with highly active relapsing MS and 36 with progressive MS. The fatal event occurred after the June 2026 data cutoff used for the presentation.
Is zola-cel available as an MS treatment?
The source describes zola-cel as an investigational therapy studied in phase I research. It does not report approval for routine MS treatment; patients should discuss treatment decisions with a qualified health professional.
Source: rss
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