Experimental CAR T-cell therapy shows promise in early MS trial
Most patients receiving zola-cel have stable or improved disability scores
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Most people with relapsing or progressive forms of multiple sclerosis had stable or improved disability scores after receiving a single infusion of the experimental CAR T-cell therapy zolacabtagene autoleucel, according to interim trial resullts.
- An early trial of the experimental CAR T-cell therapy zola-cel showed stabilized or improved disability scores in MS patients.
- The findings also suggest that the higher dose may reduce the need for ongoing MS medications.
- The single-infusion treatment aims to deplete B-cells, though safety concerns remain.
Most people with relapsing or progressive forms of multiple sclerosis (MS) had stable or improved disability scores, along with signs of reduced disease activity, after receiving a single infusion of the experimental CAR T-cell therapy zolacabtagene autoleucel (zola-cel).
That’s according to interim results from a Phase 1 clinical trial, called Breakfree-2 (NCT06220201), which tested two zola-cel dose levels in 66 adults with ongoing MS disease activity or whose disability continued to worsen despite treatment. The findings also suggest that the higher dose may reduce the need for ongoing MS medications.
However, safety concerns remain. While most reported side effects were mild or moderate, serious neurological complications occurred, and one participant died of pneumonia, a severe lung infection, after receiving additional treatment for neurological symptoms. Whether the therapy contributed to the fatal outcome is being investigated.
The reported death occurred after Bristol Myers Squibb (BMS), the therapy’s developer, had already paused enrollment in its trials of zola-cel for autoimmune diseases following safety concerns detected during routine surveillance. BMS said the death was unrelated to the issues behind the pause, and that no other deaths had been reported among 190 people treated across its Phase 1 studies of zola-cel in autoimmune diseases.
The findings were presented at MSToronto 2026, the 10th joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis, held last week in Toronto, Canada.
“The Breakfree-2 data demonstrate clinical potential for zola-cel in multiple sclerosis, showcasing the opportunity for treatment-free remission in patients who have depended on chronic therapies for years,” Lynelle B. Hoch, president of BMS’ Cell Therapy Organization, said in a company press release. “We are advancing zola-cel with the goal to redefine autoimmune care with a single, transformative treatment.”
Zola-cel targets B-cells involved in MS
In MS, the immune system mistakenly attacks healthy tissue in the brain and spinal cord, causing inflammation and nerve damage. Although available disease-modifying therapies (DMTs) can reduce disease activity and slow disease progression, some people continue to experience relapses or worsening disability despite treatment.
“People living with relapsing and progressive forms of multiple sclerosis need treatment options that address the underlying disease while helping control relapses and preserve function,” said Jeffrey A. Cohen, MD, a professor of neurology and staff physician at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis who presented the findings at the meeting.
Zola-cel, also known as BMS-986353, aims to address this need by targeting B-cells, immune cells involved in MS.
The therapy involves collecting a patient’s T-cells, another type of immune cell, and modifying them in the lab to carry an engineered protein called a chimeric antigen receptor (CAR). The CAR directs the T-cells to recognize a protein found on B-cells called CD19.
Once infused back into the bloodstream, the modified T-cells seek out and destroy B-cells, which is expected to reduce the immune system’s attack on the brain and spinal cord and provide lasting disease control after a single infusion.
6 of 7 patients had no signs of disease activity after at least 6 months
Breakfree-2 included 30 adults with highly active relapsing MS and 36 with progressive forms of MS. Participants had previously received a median of two DMTs. Before receiving zola-cel, they underwent a low-dose chemotherapy treatment to eliminate existing immune cells and make room for the CAR T-cells. The first six participants received 5 million CAR T-cells, while the remaining 60 received 10 million cells.
After at least six months of follow-up, six of seven evaluable participants (86%) with relapsing MS who received the higher dose had no evidence of disease activity, meaning they experienced no relapses, no worsening disability, and no new MRI activity.
Among the eight participants evaluated in the higher dose group, one had stable scores on the Expanded Disability Status Scale (EDSS), a standard measure of MS-related disability, and seven had improved scores, meaning less severe disability.
Among the 24 participants with progressive MS in the 10 million dose group evaluated after at least six months, 22 (92%) had stable or improved EDSS scores, despite worsening disability before treatment. All 24 also showed no new disease activity on MRI scans, and several experienced improvements in walking function and hand dexterity.
These data suggest that CD19-directed CAR T cell therapy may offer a new approach to treating multiple sclerosis. While more research is needed, the potential to control relapses, stabilize disability and reduce reliance on disease-modifying medications is encouraging.
At their latest follow-up, all 60 participants who received the higher zola-cel dose remained off DMTs, including nine followed for more than a year. Tests also confirmed B-cell depletion, suggesting zola-cel was working as intended.
Cytokine release syndrome (CRS), an acute inflammatory reaction that can be triggered by CAR T-cell therapies, occurred in 28 participants (42.4%), while five (7.6%) developed immune effector cell-associated neurotoxicity syndrome (ICANS), a neurological complication. All but one case were mild or moderate and resolved typically within two days. The exception was a severe ICANS episode, which resolved within four days.
On day 17 after zola-cel infusion, the participant who died developed movement-related symptoms, including rigidity and tremor, that did not respond to initial treatment. Doctors then administered high-dose cyclophosphamide, a chemotherapy drug, to target the CAR T-cells, but the participant subsequently developed pneumonia and died the following day, 44 days after receiving zola-cel.
“These data suggest that CD19-directed CAR T cell therapy may offer a new approach to treating multiple sclerosis,” Cohen said. “While more research is needed, the potential to control relapses, stabilize disability and reduce reliance on disease-modifying medications is encouraging.”
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