BMS Reports Death in Phase 1 Zolacabtagene Autoleucel MS Study

Bristol Myers Squibb (BMS) disclosed that a patient with highly active relapsing multiple sclerosis (haRMS) died of septic pneumonia 44 days after receiving zolacabtagene autoleucel (zola-cel; BMS-986353). Zola-cel is an investigational autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, and the patient was in the phase 1 Breakfree-2 study. The death occurred after the data cutoff. BMS reported it on October 23, 2026, along with interim results presented at MSToronto 2026, the 10th Joint ACTRIMS-ECTRIMS Meeting.¹

What led to the fatal event?

According to BMS, the patient developed late-onset motor symptoms after infusion that were not ICANS (non-ICANS). These did not resolve with intermittent corticosteroids and intravenous immunoglobulin. The patient's CAR T-cell expansion was consistent with that observed across the study. The patient was then treated with high-dose cyclophosphamide, developed septic pneumonia, and died the following day.¹ BMS reported no other grade 5 events across its zola-cel autoimmune programs, which include 190 patients treated in phase 1 studies.¹

"These data suggest that CD19-directed CAR T cell therapy may offer a new approach to treating multiple sclerosis," said Jeffrey A. Cohen, MD, professor of neurology and staff physician at the Cleveland Clinic Mellen Center, in a company press release.¹ "While more research is needed, the potential to control relapses, stabilize disability, and reduce reliance on disease-modifying medications is encouraging."

How does the case compare with prior CAR T experience?

Non-ICANS neurotoxicities are delayed neurologic syndromes distinct from ICANS. They have been described mainly with CAR T-cell therapy directed at B-cell maturation antigen (BCMA) in multiple myeloma. Blumenberg et al² linked potentially fatal non-ICANS neurotoxicities after ciltacabtagene autoleucel (Carvykti) to high CAR T-cell expansion and long persistence. They described cyclophosphamide, used to ablate CAR T cells, as an effective strategy for steroid-refractory cases.² In the zola-cel case, BMS reported CAR T-cell expansion consistent with that observed across the study.¹

Infection is a known risk of CD19-directed B-cell depletion in autoimmune disease. Müller et al³ reported a case series of 15 patients with lupus, myositis, or systemic sclerosis treated with CD19 CAR T cells. One patient had pneumonia requiring hospitalization, and B-cell aplasia lasted a mean of 112 days.³

What did the broader MS data show?

Breakfree-2 enrolled 66 patients comprising 30 with haRMS and 36 with progressive MS (PMS). All had ongoing disease activity or worsening disability despite a median of 2 prior disease-modifying therapies (DMTs).¹ Cytokine release syndrome occurred in 42.4% of patients (28/66). Most cases were grade 1 (36.4%), and they resolved in a median of 2 days. ICANS occurred in 7.6% (5/66). One grade 4 event, in a patient with PMS, resolved within 4 days with corticosteroids and anakinra.¹

All 60 patients treated at dose level 2 remained off DMTs at last follow-up, including 9 with more than 12 months of follow-up. Among 32 evaluable patients, 6 of 7 with haRMS met no evidence of disease activity criteria at week 26 or later. Of the patients with PMS, 22 of 24 (92%) showed stable or improved disability, and all 24 had no new MRI activity.¹

The results build on an earlier report in which 2 patients with progressive MS were each treated individually with a fully human CD19 CAR T-cell therapy. Neither developed ICANS, even though CAR T cells were detected in their cerebrospinal fluid.⁴

What are the limitations?

Breakfree-2 is a single-arm, dose-escalation phase 1 study with no control group, and the efficacy analyses involve small evaluable subsets. The results are interim conference data and have not been peer reviewed. The fatal event occurred after the data cutoff, and the only details available are the company's description. BMS did not name a cause of death beyond septic pneumonia. The release does not allow for one to determine whether cyclophosphamide-based CAR T-cell ablation added to the infection risk in this case. Longer follow-up is needed to show how long B-cell depletion lasts in MS and what infection risk comes with it.

References

1. Bristol Myers Squibb. Bristol Myers Squibb presents results from phase 1 Breakfree-2 study of zolacabtagene autoleucel (BMS-986353) in patients with highly active relapsing and progressive forms of multiple sclerosis at MSToronto 2026. Press release. Published October 23, 2026. Accessed October 26, 2026. https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Presents-Results-from-Phase-1-Breakfree-2-Study-of-Zolacabtagene-Autoleucel-BMS-986353-in-Patients-with-Highly-Active-Relapsing-and-Progressive-Forms-of-Multiple-Sclerosis-at-MSToronto-2026/default.aspx
2. Blumenberg V, Puliafito BR, Graham CE, et al. Cyclophosphamide mitigates non-ICANS neurotoxicities following ciltacabtagene autoleucel treatment. Blood. 2025;145(23):2788-2793. doi:10.1182/blood.2024028172
3. Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-cell therapy in autoimmune disease—a case series with follow-up. N Engl J Med. 2024;390(8):687-700. doi:10.1056/NEJMoa2308917
4. Fischbach F, Richter J, Pfeffer LK, et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med. 2024;5(6):550-558.e2. doi:10.1016/j.medj.2024.03.002