Bristol Myers Squibb (BMS) has disclosed a patient death in its early-stage Breakfree-2 trial studying zolacabtagene autoleucel, an investigational, autologous CD19-directed CAR T cell therapy, in patients with relapsing or progressive forms of multiple sclerosis (MS).

The death was disclosed as part of a broader data readout presented in an oral presentation at MSToronto 2026 and follows the company’s decision to place a voluntary pause on zola-cel studies back in September.

What happened to the patient?

The patient, who had highly active relapsing MS, died of septic pneumonia one day after receiving high-dose chemotherapy and 44 days after zola-cel infusion.¹ According to BMS, the patient experienced late-onset, non-ICANS motor symptoms following infusion that did not resolve with intermittent corticosteroids and intravenous immunoglobulin.

Although the patient’s CAR-T cell expansion was consistent with that observed across the study, physicians administered high-dose cyclophosphamide, after which the patient developed septic pneumonia and died the following day. A BMS spokesperson told Reuters, “The patient had a late onset side effect, a series of other complications and was heavily pretreated prior to CAR T, confounding our ability to determine the root cause of the issue.”² BMS says the death was unrelated to the earlier voluntary pause and that no additional Grade 5 events have occurred across any zola-cel autoimmune disease program, which has treated 190 patients in Phase I studies to date.

How does this connect to the broader safety pause?

BMS voluntarily paused studies of zola-cel in September to review safety data, a decision that followed Novartis halting eight clinical trials of its own experimental cell therapy after reported deaths.¹ The company says it is working with the FDA to restart all zola-cel studies and is aiming to resume enrollment in early 2027.¹

What did the rest of the trial data show?

The Breakfree-2 study enrolled 66 patients, 30 with highly active relapsing MS and 36 with progressive MS, who had ongoing disease activity or worsening disability despite a median of two prior disease-modifying therapies.¹ The study’s primary endpoint was safety, with efficacy as a secondary measure.

Overall, 42.4% of patients (28 of 66) experienced cytokine release syndrome, the large majority Grade 1, resolving in a median of two days. Immune effector cell-associated neurotoxicity syndrome occurred in 7.6% of patients (5 of 66), mostly Grade 1 or 2 and resolving in a median of two days; one Grade 4 case occurred in a progressive MS patient and resolved within four days after treatment with corticosteroids and anakinra.¹ BMS says the majority of adverse events were brief and reversible, consistent with previously reported zola-cel data.

On efficacy, all patients treated at dose level 2 (60 of 60) remained off disease-modifying therapies at last follow-up, including nine patients followed for more than 12 months.¹ Among evaluable patients at dose level 2 with at least 26 weeks of follow-up, six of seven relapsing MS patients met criteria for no evidence of disease activity, and 22 of 24 progressive MS patients showed stability or improvement in disability progression despite prior worsening at baseline.

BMS frames the data as supportive of zola-cel’s broader potential despite the fatality. “BMS is at the forefront of cell therapy science, pioneering a new era by exploring the potential for immune reset in patients living with autoimmune diseases,” says Lynelle B. Hoch, president of the Cell Therapy Organization at Bristol Myers Squibb. “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.”

Jeffrey A. Cohen, professor of neurology and staff physician at the Cleveland Clinic’s Mellen Center, offers a more measured outside assessment. “These data suggest that CD19-directed CAR-T cell therapy may offer a new approach to treating multiple sclerosis,” he says. “While more research is needed, the potential to control relapses, stabilize disability and reduce reliance on disease-modifying medications is encouraging.”

What’s next?

With BMS now coordinating directly with the FDA on a restart timeline targeting early 2027, the company’s ability to resolve outstanding safety questions will likely determine how quickly, and how broadly, zola-cel can advance toward later-stage development in MS and other autoimmune diseases.

Sources

1. 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 Bristol Myers Squibb October 23, 2026, https://www.businesswire.com/news/home/20261022949204/en/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
2. Bristol Myers discloses patient death in early-stage cell therapy study Reuters October 23, 2026, https://www.reuters.com/legal/litigation/bristol-myers-discloses-patient-death-early-stage-cell-therapy-study-2026-10-23/