Turn on cookies to sign in
Signing in saves your progress to your Curie account. We can only do that with cookies on — turn them on to continue.
A phase 1 trial of zolacabtagene autoleucel (zola-cel), a CAR T-cell therapy targeting B cells, showed encouraging efficacy in both relapsing and progressive MS — but one patient died of septic pneumonia 44 days post-infusion. Most side effects were mild and short-lived, and 92% of progressive MS patients showed stable or improved disability. Researchers say the therapy holds real promise, but more work is needed to understand the risks.
CAR T-cell therapy is making inroads into multiple sclerosis treatment, and the latest data from the phase 1 Breakfree-2 trial of zolacabtagene autoleucel (zola-cel) offers both hope and a sobering reminder of the risks. The study enrolled 57 patients — 21 with highly active relapsing MS and 36 with progressive MS — all of whom had continued disease activity despite prior therapies. The therapy works by deeply depleting B cells in both blood and tissues, then allowing a "reset" with naïve B cells, a mechanism that goes beyond what existing MS drugs can achieve.
Efficacy signals were strong: 6 of 7 evaluated relapsing MS patients showed no evidence of disease activity at week 26, and 92% of progressive MS patients had stable or improved disability — with no new MRI activity in any of them. All patients on dose level 2 were off disease-modifying therapies at follow-up. However, one patient died on day 44 after developing severe extrapyramidal symptoms and subsequently receiving high-dose cyclophosphamide, which led to septic pneumonia. The cause remains under investigation.
Key Takeaways:
Why it matters: CAR T-cell therapy could represent a paradigm shift in MS treatment — potentially offering durable disease control with a single infusion. But the one fatal case underscores that this approach carries rare but serious risks, and larger, controlled trials are essential before broader use.
