"One and Done" Therapy for Multiple Sclerosis: New Trial With Impressive Results

A randomized trial demonstrated that “resetting” the immune system may be the key to stopping multiple sclerosis in its tracks.

This week, I want to talk about a really remarkable piece of work. But it’s not remarkable in the way a lot of the reporting is saying. The trial appears in the Journal of the American Medical Association.

Dr. Richard Burt, Lead Author

Before we get started, let’s parse the title a bit. This is a randomized trial comparing nonmyeloablative hematopoietic stem cell transplantation vs. disease modifying therapy for relapsing-remitting MS.

That’s a mouthful – but it’s where a lot of people get this study wrong.

When you hear “stem cell therapy” you tend to think about miracle cures for a variety of crazy diseases – using your own cells to regrow damaged tissue. This is definitively NOT what this study was about. I asked lead author Dr. Richard Burt to dispel the hype:

“The therapy – the Cytoxan and ATG given over five days – is designed to knock your immune system down”.

That’s right this study used chemotherapy, cyclophosphamide, to nearly wipe out an individual’s bone marrow. The stem cell transplant was just there to help reboot the immune system afterwards. Dr. Burt told me the therapy would probably work without the stem cell infusion, it would just be riskier.

So this is actually a study of an old therapy – cyclophosphamide - applied in a new way – not a new therapy.

Kaplan-Meier curves that make epidemiologists go “dammmmnnn”.

Dr. Burt and his team randomized 110 individuals with relapsing remitting MS, the most common form of the disease, to this chemotherapy protocol or conventional disease-modifying therapy – that could range from various interferons to more novel biologics.

After about 2 and a half years, 3 of the 55 individuals in the cyclophosphamide group had progression of disease, compared to 34 out of 55 patients in the standard therapy group.

You don’t see Kaplan-Meier curves that look this good all that often, folks.

My QOL is increased by you, dear reader.

And that’s not all.

Take a look at the quality of life numbers. 

Dramatically better in the cyclophosphamide group. That’s not too surprising, actually. One of the major advantages of the cyclophosphamide protocol is that it’s one and done – no need for further therapy. Here’s Dr. Burt again.

“So one thing we’re very careful [about] in this paper [is] we don’t talk at all about cure and I don’t want to imply that, but you know very few by five years relapsed or progressed in the vast majority with no evidence of disease activity”.

Can someone turn the MRI lesion volume down?

Functional status decreased in the usual therapy group, as expected, but actually improved in the cyclophosphamide group. And if you’re the type of person who wants more objective data, T2-weighted lesion volume on MRI decreased by 30% in the cyclophosphamide group compared to an increase of 34% in the usual care group.

Why does this work? We’re not totally sure. Dr. Burt believes that the chemotherapy essentially resets the immune system – allowing tolerance to develop. In other words, fixing the immune system in patients with MS might work how you fix your internet router – turn it off and on again.

Alright, I’ll give you some caveats here.  First, we aren’t sure what the appropriate timing of this therapy is. Patients in this study had to have two flares in the past year and a moderate baseline disability score. This probably shouldn’t be the go to therapy for very early or mild disease. Similarly, there is no evidence that this protocol will help in progressive MS.

Ocrelizumab is like the new kid at school who gets really popular, and then the old cool kid (cyclophosphamide) reasserts itsself.

The other major issue is that this study has been running for a long time- about a decade. In that time a couple of novel therapies, including ocrelizumab have entered the scene. Patients on ocrelizumab were excluded from this study. Dr. David Hafler, chief of neurology here at Yale, was quite impressed with the results in this study, but suspects that you may see similar effects with ocrelizumab.

Indeed, a large randomized trial of ocrelizumab appearing in the New England Journal seems to have similar rates of progression as we see in the cyclophosphamide group here.

With Ocrelizumab costing $65,000 per year, and Dr. Burt’s chemotherapy protocol running at a one-time cost of $125,000, the jury is still out where the most bang for the buck is. But the real winners here are patients with MS, who now have more options than ever before to hit the reset button on a devastating disease.