A treatment that’s almost too good to be true

Dermatologist Dr. David Fiorentino is excited about the possibilities of cell therapies to treat autoimmune conditions like dermatomyositis (DM). In collaboration with rheumatologists and bone marrow transplant specialists at Stanford University, he is conducting a small, phase 1b clinical trial testing KYV-101, a CAR T cell therapy that targets a protein called CD19 on the surface of B cells, that is being developed by the German biopharmaceutical company.

“We’ve been working with the company, Kyverna, for quite a while,” Fiorentino says. “They have been working with a group in Germany led by Georg Schett, who have been the early pioneers for using anti-B cell therapy in lupus, myositis, and other autoimmune diseases.”

Fiorentino, who is one of the world’s leading experts in DM and is a member of TMA’s Medical Advisory Board, is eager to gain experience examining the efficacy of such a treatment strategy, and to understand how this cell therapy affects the different forms of DM, including clinically amyopathic and those with various autoantibodies (including MDA5). As a dermatologist, he is especially interested to see how the skin responds separately from muscle and other symptoms.

“The course of skin, muscle, and lung disease don’t necessarily progress in parallel,” he says. “We use slightly different therapies to treat skin than we do lung or muscle, and there’s very little experience looking at what happens to skin disease with DM patients who are given the CD19 CAR T therapy.”

Interestingly, while most clinical trials in myositis are required by the FDA to include patients with muscle weakness, this trial specifically allows those patients who have no muscle symptoms but do have severe skin disease.

“What we’re trying to do is give the patient back their immune system that they had before they got autoimmune disease.” – Dr. David Fiorentino

Part of the excitement about CAR T cell therapy is related to expectations that this treatment has the promise of sustained disease remission, and, in some cases, what amounts to a cure due to an immune system “reset.” It’s understandable. The words “remission” and “cure” are not words often heard in the myositis community. Fiorentino is cautious, though.

“Honestly I don’t think of it as one and done,” he says. “I don’t think this therapy is necessarily going to be a cure in all cases for all patients. I believe it’s possible there could be long-term, durable remissions in some patients, but we just don’t know. There is always the potential for relapse or inadequate efficacy in some patients.”

So far there have only been a handful of people in the world who have received this unique, individualized, and very expensive treatment. Still, early reports indicate that it is remarkably effective. Patients have regained most if not all of their muscle strength and function within about three months, fatigue fades, and they feel better. Lung inflammation diminishes or even improves. Typically, even autoantibodies seem to disappear. And most—not all, though—have come off their medications completely.

“We haven’t seen these kinds of responses with other kinds of therapies,” Fiorentino says. “So there’s understandably a lot of excitement. But there will be a long process of trying to find out what’s the most effective, fast, safe, tolerable way to implement it. And then within a myositis diagnosis, there are many different subtypes to explore. So it’s early days.”

Dermatologist Dr. David Fiorentino is a myositis specialist at Stanford University and serves on TMA’s Medical Advisory Board. Read more about cell therapy as a treatment for autoimmune disease in the winter issue of TMA’s The Outlook magazine.