ECTRIMS 2025 | Further findings from a Phase I trial of CAR-T in MS: patient-reported outcomes

So what happened next? So they were discharged. And I have to say at this point, we didn’t know what to expect. This is something that’s just not been done or observed so closely before. We don’t know the phenotype. We don’t know the clinical course. The research that we’re doing is intended to provide the foundation for that with information that we can then share with our colleagues nationally and internationally so that downstream studies can be properly designed and patient safety can be optimized. So one thing we didn’t expect is that the subjects would feel really run down and experience a lot of malaise. And if anything, I’d say their general experience was that they felt like they had taken a step backwards. In MS patients who have received IV therapy before, some have received steroids. And the use of steroids, especially early in the MS course, can give them a very abrupt sort of next day boost in energy or eradication or partial eradication of symptoms of an MS attack. So I think it could be natural for patients who were just given an infusion of a medicine that they knew was a big deal to feel as if they might feel better overnight. I mean, that’s their hope, of course. Wouldn’t it be true for all of us? But that’s not what happened. They actually felt like their energy levels declined. And they, on average, had about three months after infusion, not of serious adverse reactions, no cytokine release syndrome, no ICANS. We monitored blood counts extremely closely, looking at white blood cells, platelet levels, myeloid cells. All of those stayed relatively stable. We followed assiduously for infection and didn’t see evidence of secondary infection in that period of time. We have since. But yeah, they felt like they had malaise for three months. And then abruptly, just as abruptly as their fever had come on, it seemed as if overnight things turned and they woke up. And the most remarkable thing happened. As an important reminder, a Phase I study, and again, this to our knowledge is the first prospective study that takes on this subject. A Phase I study means a few patients with close attention to safety. That’s its purpose. So I want to stop short of making any therapeutic claims that you can’t make reliable therapeutic claims on the basis of small numbers of patients observed or treated in a single center, not reproduced by colleagues that are widespread, you know, either within the country or internationally. So what we’ve seen on a clinical basis has to be taken with a grain of salt. But that said, it’s been remarkable what we’ve seen, in my opinion. I haven’t seen anything like it in all my years of practice, and I’ve been at this for a while. So one thing that’s important to remember is that the patients that we enrolled in the study were not, in this case, young patients who had just had brand new onset of MS, who had active relapsing-remitting disease. There are plenty, many, more than 25 approved immunotherapies or disease-modifying therapies for patients of relapsing MS of that type. And so it was appropriate using an experimental immunotherapy to target patients for whom there was no other approved or proven therapy. And so our study enrolled patients between the ages of 18 and 70 who were more advanced in their MS and who didn’t have relapsing disease anymore. They were having worsening MS. They were slowly losing strength or balance. They were losing the ability to walk distances or perform their independent activities of daily living. And yet they still maintain function. But in all cases, they had been prescribed treatment that just simply wasn’t holding them. Every one of them who came to us said, I’m doing everything the doctor is telling me. I’m still losing ground. I’m starting to worry that the things I love and care about so much, like being able to participate and be a presence for my family, being able to attend my child’s soccer games or football games to our European Union friends, but being there for family or being able to work full time, they felt that they might be losing that. So this cohort, in the jargon of our subspecialty, are non-relapsing, worsening cases of multiple sclerosis. That’s the cohort that we treated. There were no early cases of relapsing disease. All of my colleagues in this field will recognize at once that this is one of the most difficult therapeutic challenges because our therapies, such as the ones approved today, it can be said generally they can reduce the risk of new attacks, but the evidence that they slow down or reverse worsening or reverse accumulating weakness from the disease is sparse and sometimes not satisfactory. So to see any effect in this cohort of patients with non-relapsing, worsening MS that hasn’t responded to the best therapy we have otherwise is honestly not something that we expected. We hoped at best we might see some stabilization, some leveling off, and the subjects themselves all said they’d be quite content with that if this relentless progression they were suffering from could just be paused or slowed or leveled off. I mentioned just a moment ago that about three months after infusion, there was an abrupt change, like a switch almost overnight. And the thing that we noticed first was an abrupt increase in energy. Fatigue is the most common symptom that MS patients experience. Not every MS patient does, but it’s the most common if you were to talk to hundreds or thousands of MS patients. Fatigue is usually on their list. And it’s a profound fatigue. But for those listeners that haven’t experienced MS themselves personally, if they’ve come down with a really bad cold, like a really bad one, they’ll know that maybe that day or two before they develop a sore throat or sniffles or cough, they feel like they’re so wrung out of energy, it’s hard to stand. That’s more similar to the fatigue of what MS patients feel. And they learn to live with it a bit, but it’s really difficult. Well, every subject that we talked to said that that fatigue lifted. And this is new to us. We haven’t seen this kind of phenomenon. An MRI doesn’t measure fatigue. And as much as we’ve tried to look for biomarkers that might be associated with this fatigue and lassitude that’s characteristic of MS, we haven’t found any marker, any blood test that can help us gauge the fatigue a patient is feeling. So what we did in this study was we used patient-reported outcomes. Those are subjective. They’re not truly scientific, but they’re important because they speak to the patient’s personal experience. We employed a quality of life survey that gets at fatigue, that’s been validated. It’s widely accepted in our community. And we were seeing improvement on this scale of between 8 to 12 points, which, if you don’t know the scale, is a profound improvement. What might make more sense is for me to share the story that these patients, I believe all of them, were having to take naps or two every single day of their lives. They’d get up, they’d be able to walk around, do a couple things for a couple hours. They’d have to take a nap and then maybe a second nap every day just to maintain energy. Suddenly they didn’t need naps at all. And they told us it had been 15, 20 years since they didn’t have to take a nap. Several of them told us that they felt their energy levels were the same as before they even got MS. Suddenly they were able to go about their day, be with their family, be effective at work, and maintain their energy and alertness all day long. We had never seen anything like that before. And these are small numbers. So again, it’s really important that we keep even, that we employ equipoise, we not make too much of this. But it’s an astonishing result to see this level of improvement of fatigue. We did see that and we continue to see that to this day. The first subject has been now well into one year past her initial infusion.

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