Objective:

The article examines the objective, findings, and clinical context described in BMS Details Patient Death in Zola-Cel Multiple Sclerosis Trial.

Approach:

• Therapy: Zolacabtagene autoleucel (zola-cel) is an investigational autologous CD19-directed CAR T-cell therapy made using BMS’s NEX-T platform.
• Study: Breakfree-2 is a single-arm, dose-escalation study involving 66 people with highly active relapsing or progressive MS that continued to worsen despite treatment.

Key Findings:

• A participant with highly active relapsing MS developed delayed motor symptoms after zola-cel. BMS said the symptoms were not classified as ICANS and did not resolve after intermittent corticosteroids and intravenous immunoglobulin.
• After receiving high-dose cyclophosphamide, the participant developed septic pneumonia and died the following day, 44 days after infusion. The event occurred after the Breakfree-2 data cutoff.
• BMS reported no other deaths among 190 patients treated in its Phase I zola-cel autoimmune-disease studies. Enrollment in the autoimmune program had been paused following reports of transient inflammatory events.
• In Breakfree-2, cytokine release syndrome occurred in 28 of 66 participants: 24 cases were grade 1 and four were grade 2; all resolved within a median of two days. Five participants developed ICANS, including one grade 4 event that resolved within four days af…
• All 60 participants treated at the second dose level remained off disease-modifying therapies at their latest assessment; nine had more than one year of follow-up.
• Among participants with at least 26 weeks of follow-up, six of seven evaluable participants with highly active relapsing MS had no relapses, disability progression, or new MRI activity. Disability scores were stable or improved in all eight evaluable participa…

Interpretation:

Jeffrey Cohen of Cleveland Clinic said the findings suggest CD19-directed CAR T-cell therapy may offer a new approach to MS, while noting that more research is needed.

Limitations:

• Breakfree-2 was a single-arm, dose-escalation study; the reported disease-control findings were interim and based on small evaluable groups.
• The fatal event occurred after the Breakfree-2 data cutoff.

Sources:

• Article context provided