Patient death reported in BMS CAR-T trial for MS amid early efficacy signals

Bristol Myers Squibb disclosed interim safety and efficacy results from the multiple sclerosis cohorts of the phase 1 dose-escalation Breakfree-2 study evaluating zola-cel, an autologous CD19-directed CAR-T cell therapy, in patients with highly active relapsing MS (haRMS) and progressive forms of MS (PMS).

According to BMS, after the data cutoff, one patient with haRMS experienced a fatal event of septic pneumonia. Following zola-cel infusion, the patient had experienced late onset, non-ICANS motor symptoms that were not resolved by treatment with intermittent corticosteroids and intravenous immunoglobulin. High-dose cyclophosphamide was administered and the patient developed septic pneumonia and died the following day, 44 days after infusion.

BMS says no additional Grade 5 events have been reported across all zola-cel programs in autoimmune diseases, which include 190 patients treated in phase 1 studies. In the Breakfree-2 study, 42.4% of patients experienced cytokine release syndrome (CRS) and 7.6% developed immune effector cell-associated neurotoxicity syndrome (ICANS). Most events were mild and resolved within a median of two days, although one patient with progressive MS experienced Grade 4 ICANS that resolved within four days following treatment with corticosteroids and anakinra.

Secondary endpoints included measurements of efficacy, with zola-cel demonstrating potential for immune reset via complete B-cell depletion. At last follow up, all patients treated at dose level 2 (60/60) remained off disease-modifying therapies, including nine patients with more than 12 months of follow-up.