Episode 477: One Year After CAR T-Cell Therapy with Jan Janisch-Hanzlik

0:18 It's October 20th, and we have a lot to talk about. I'm in Toronto, Canada, where MS Toronto 2026, the largest MS research conference in the world, gets underway tomorrow. Somewhere in the neighborhood of 9,000 MS researchers and clinical specialists are expected to attend this joint meeting of the America's Committee for Treatment and Research in MS and the European Committee for Treatment and Research in MS. And I hope you plan on joining us, either in person or online, this Friday at 3 p.m. Eastern Time for Patient Community Day. This is a great opportunity to hear from some of the top MS experts in the world as they share updates from MS Toronto 2026 in plain, easy-to-understand English.

1:07 There's even an opportunity for you to ask questions. There's no charge to participate in Patient Community Day, and you can register at ektrumspatientcommunity.eu. You'll find that link in today's show notes. One of the topics that I know we'll be hearing about at MS Toronto 2026 is CAR-T cell therapy. It's a therapy that's currently used to treat certain cancers, and there are clinical trials underway to determine whether it's effective in treating MS. Last year, we met Jan Janisch-Hanzlik on the podcast. Jan was the first MS patient to receive CAR-T cell therapy as part of a clinical trial, and Jan took us through what the procedure was like and how she was already seeing improvement in several of her MS-related symptoms.

1:57 Today, Jan is back to share a one-year update with us. And before we hear from Jan, there are a couple things I want to point out. First, as you hear about Jan's experience, please keep in mind that people with MS respond differently to any treatment. Jan's just one individual, and her response to CAR-T cell therapy won't be what everyone experiences. I also want to mention that last month, two major pharmaceutical companies paused their CAR-T cell therapy clinical trials after three trial participants with MS died. I asked Jan about that, and she has some definite thoughts that she shares during our conversation.

2:40 But before we get to my conversation with Jan JJanisch-Hanzlik , I want to remind you that if you live in the United States, we're just two weeks away from Election Day. And make no mistake, your health care and future funding for medical and scientific research are on the ballot. Here's a reality check on the current congressional landscape. In the current Congress, one party decided not to extend enhanced tax subsidies for millions of Americans who get their health insurance through the online health insurance marketplace at healthcare.gov. gov. The same party has radically remade Medicaid, reducing funding to every state, and raising requirements that can be particularly difficult for someone living with a disability to meet.

3:29 The result of all this partisan congressional action has been clear. Between 8 and 10 million American men, women, and children have lost their health insurance this year. And that's only this year. In the current Congress, we saw one party eliminate all funding for the MS Research Program. Fortunately, a significant lobbying effort on the part of MS activists and the National MS Society brought the MS Research Program back from the dead, and 75% of that funding was made available a year later. You know, when I initially thought about addressing the upcoming election on this podcast, I wanted to maintain a nonpartisan perspective And I realize everything I just said doesn't sound nonpartisan.

4:17 The name of this podcast is RealTalk MS, and these draconian cuts in funding, this philosophy of relegating people living with MS and other chronic illnesses and disabilities to the back of the bus in America, well, it's been the exclusive work of one political party, and I'm not going to try to spin that any differently, because then I'd be lying to you. I'm not here to tell you how to vote or who to vote for, but I will strongly suggest that every person living with MS or any chronic illness should vote in their own best interest, and I believe that is being nonpartisan.

4:58 If you'd like to arm yourself with information as you get ready to vote, I hope you'll make time to watch the video replay of the National MS Society's webinar entitled MS Advocacy in Action, What the 2026 Elections Could Mean for Healthcare Policy and Access to Care. The webinar features Nathaniel Wexel, the healthcare reporter for The Hill, and a discussion about the election landscape, the legislative landscape ahead, and what the results could mean for people affected by MS. And you'll find a link to the YouTube video replay of this webinar in today's show notes. I also think it's important for you to drill down to your state, your community, to know how your congressional representatives and senators have voted on major legislation impacting access to health care over the past two years.

5:51 All you have to do is visit realtalkms.com and check out the Congressional Health Care Access Report Card. Just click on your state and you'll see exactly how well your congressional representatives and senators did when it came to supporting the health care issues that affect you and your family. It's an easy way to help you make an informed decision when you cast your vote. This could be the most consequential election in our country's history, and I hope 100% of the Real Talk MS listener community in the United States is planning to support the candidates that support them and vote on behalf of their own self-interest.

6:37 In CAR-T cell therapy, blood is taken from the patient or a healthy donor, much as you would facilitate a blood donation. This blood is sent to a lab where the white blood cells, or T-cells, are separated out and reprogrammed to carry a receptor designed to fight a particular condition. This receptor is known as a chimeric antigen receptor, or CAR. Over the course of several weeks in the lab, these fortified T-cells multiply until there are millions of them, and then they're reintroduced to the patient through an intravenous infusion. Jan Janisch-Hanslick was the first MS patient to receive CAR T cell therapy as part of a clinical trial, and we met Jan last year in episode 424 of Real Talk MS when she gave us a firsthand report on how she was responding to this treatment.

7:32 This week, Jan is back with an update on how she's responding one year later, and in a moment, we'll welcome Jan Janisch-Hanslick back to the podcast. Just over a year ago, Jan Janisch-Hanzlik became the first person in the world to receive allogenic CAR-T cell therapy to treat MS. This therapy uses T cells from a healthy donor that have been genetically modified to target and destroy a protein on the surface of B cells. These are the immune cells that trigger MS inflammation. Just like stem cell therapy, the theory is that once the B cells have been destroyed, after just a single treatment, The immune system will reset itself and behave in what we can think of as a more normal, healthy way.

8:21 Last October, we talked with Jan about how she was responding to her treatment. If you happen to miss that episode, you can check it out at realtalkms.com slash 424, and we'll include that link in today's show notes. It's been a little over a year since Jan received her CAR-T cell therapy, and today she's here to share an update on how she's continuing to respond to this experimental therapy. Welcome back to the podcast, Jan. Thank you. I'm very glad to be here. When we last spoke just a few months post-infusion, you were experiencing encouraging progress. Now that you've reached the full one-year mark, how are you feeling physically, and how does your everyday baseline compare to where you were a year ago?

9:09 So I just reached my 15-month mark here in August, and I feel so much better. I feel that my gait has improved. I am not nearly as tired as I used to be. My sensation has improved. I still walk with the cane outside of the house just for distances, just to be on the safe side. I can say that there's times I will not bring my cane, but 90% of the time I have it. However, I physically feel so much better. Not only physically, but I emotionally feel better just because it's really improved my self-confidence.

9:50 As I, felt better. Just because I felt better doesn't mean I necessarily was doing better. So I was really waiting for those results to come out. And I have some really some excellent results to share here with you guys. I was about to ask what your clinical monitoring looked like. So feel free to share. Okay. So I do my testing now every three months. And for simplicity's sake, I'm just going to go from day zero, the day I received the car tee, to month 15. So on day zero, my 25-foot time walk test was 18.9 seconds and 19.0 seconds, both with using a cane.

10:40 And for anyone who is unfamiliar with that. Anything around six seconds would be normal for a 25-foot timed walk test. So you can see my gait was drastically impaired. On the 15-month mark, I had a 25-foot timed walk test of 8.1 seconds and 7.0 seconds, and both of those were without a cane. I've almost improved my walking greater than two times. That's unremarkable. The nine-hole peg test for anybody who is not familiar with that, a nine-hole peg test is just what it sounds.

11:26 You take a little peg from a little dish and you put it in the hole and you have to do that with nine of these pegs and then you take each one out individually and they time you both on your right and your left hand. And what this type of test does is it checks the upper extremity function and the hand dexterity, fine motor coordination of each of your hands. And day zero, when I did the CAR T cells, my right hand was at 22.04 seconds. My left hand was at 22.44 seconds. And here at the 15-month mark, it was 17.8 seconds. in my right hand and in my left hand it was 19.5.

12:15 We're talking it improved by a good five seconds so it really shows that the dexterity and fine hand coordination has definitely improved. And then the symbol modality test is a test where it's a sheet full of paper and it has a bunch of symbols on them. And at the top of the page, there's like a grid that shows each symbol identifies with a number. So you're giving a certain amount of time and you have to put the number down that each symbol correlates with. And believe it or not, it really is a frustrating test. But my original score was 48, and at month 15, it was 50.

13:01 And anything 30 and above is normal. And so my doctors really didn't expect to see much of a change with that because I really wasn't having much cognition-type problems. And then my EDSS breakdown, my score initially was a 6, which means that you ambulate with the cane. Your EDSS score actually has a lot to do with your ambulation. So some studies will say that it's not a very concrete tool and others say that it is. And in this study, they are using that EDSS. And so mine went from a six, which means definitely impaired, down to 4.0. So I'm independent with ambulation.

13:50 And to see that type of a change is definitely not something that you would normally see in MS. You generally just continue to digress. So when you break down those scores, my vision, my visual, the EDSS has different categories. There's visual, there's brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral. And I'll break down each one of those so it's a little easier to understand. So, the pyramidal function, it measures muscle weakness and motor function, and common findings with this is leg and arm weakness, butt drop, spasticity, difficulty getting up and down stairs, getting in and out of a chair.

14:44 And paralysis. And so my pyramidal score at the time of the testing was a four, and currently now it is a three. And so that's the one test that you really haven't seen much progress on. And that really is because I still have a lot of weakness in that right leg. I have that right leg foot drop. However, it has improved. But according to the score, it still remains a three. Then we have the cerebellar function. And that measures coordination and balance. and this two is the other score that really didn't change and that was a three and it has remained a three and that's just because my balance is still off.

15:32 When I'm walking, I can't get up and walk and talk at the same time. Turning corners, I really have to stop and think to turn and that's just because I still have quite a bit of poor balance. So we'll go into some of the great improvements. My visual field, it was a one, and it's now a zero. And the things that they're testing with the visual field is any type of vision impairment. And interestingly enough, when I went to the eye doctor, who was unaware that I was in the study, when she was doing my testing, she said to me that. My optic nerve in my left eye had shown some improvement.

16:15 And she was really quite surprised by that. And she said... I'm not sure why this is, but when I look at your previous testing, there was some damage in that optic nerve and I don't see there's still some damage there, she said, but it's not nearly to the extent, it shows improvement. And that's when I asked her, I said, are you sure you didn't hear about me? I said, I was the one that did CAR-T, it's in the same hospital system. She's, oh, that was you? And I said, yes, that was me. She said, this explains it. So she actually was going to call the drug company and let them know that even though this wasn't something they were necessarily testing, but she had seen some improvement in that. So that's quite exciting.

16:59 And then there is the brainstem function, and that assesses your cranial nerve function. So double vision, nystagmus, any facial weakness, slurred speech, difficulty swallowing, and vertigo. And so for my brainstem function, initially, it was a two and it has remained a two. However, my double vision only shows up now when I'm extremely tired. I had always had double vision. I had to wear glasses because of the double vision. I had prisms in my eyeglasses. And so those aren't necessary anymore. I still have the nystagmus, and that's exactly the reason that I still score a 2, is because when they do that test, they still see that little flicker when I'm trying to stare at an object.

17:52 Then we have sensory function, and my sensory initially was a 2. It's down to a 1, and that just measures any type of altered sensation. And so some common findings on that would be numbness and tingling, burning sensation, loss of vibration and sense, and neuropathic pain. So interestingly enough, I didn't think about this until the beginning of August, and this was before my testing was done. But I noticed that I was really having a lot more pain in my lower extremities, especially when I was going to bed. It just felt like somebody had been standing on my feet all day, standing on the tops of them. They were just so sore and they hurt.

18:34 And I could really feel pain that I hadn't felt in years. And when I did the testing, the doctor explained that's because my sensation. When they did that, I have full sensation now in my lower extremities. And so that would be the explanation for that neuropathic pain that I'm feeling. So that is the reason that I'm scored at a one, but it's a good one. I know pain is never anything good to feel, but when you haven't been able to feel pain and now you can feel it, it shows improvement. So I'm actually excited about that. And they did start me on medication at night for pain because I'm obviously feeling that pain now.

19:17 To me, the most difficult aspect of living with MS is living with the unpredictability of the disease. I'm curious, based upon the progress you've made, and some of it is absolutely stunning in a good way, has your relationship with the unpredictability of MS changed at all? Interesting that you say that. I do have a page on Facebook called MS with Moxie, and I just wrote about this same thing. And I shared my results and I wanted people to know, yes, my results look great, but that's on a good day. There's still those bad days and I still have that unpredictability.

19:59 And so before I go in and take these tests, I'll be honest with you, I am not doing anything the day before. I am not going to be up and on my feet because I want to make sure that when I go in there, I'm performing at my best. And yes, I still have those very unpredictable days. For instance, last weekend, it was a very busy weekend. I had my grandkids over. They stayed the night. By Saturday afternoon, I was just exhausted. And again, I could tell my double vision is starting to increase. My bladder that normally has been doing completely fine now that my symptoms are.

20:43 Coming back because of all of the activity that I did, all of those symptoms do creep back in there. I wouldn't say they're nearly to the extent that they were, but I would say my walking would not be at the 19 seconds it was, but I would guess that my walking would probably be at 10 seconds for a 25-foot walk, or if they were doing the nystagmus testing, that my nystagmus would be worse. I noticed that I have to wear my glasses because I do have the double vision. I need to make sure my prisms are on. So yes, there still is that unpredictability. And it's a very good question. And I want people to be aware that, yes, the results do look good, but there are definitely still those days that are just as bad as before I had CAR-T.

21:34 Recently, CAR-T cell therapy has been in the news, not for particularly good reasons. We heard Novartis was pausing their autoimmune and neurology CAR-T cell therapy clinical trials following three patient deaths related to severe hyperinflammatory complications. This news was almost immediately followed by voluntary pauses in clinical trials by Bristol-Myers Squibb. So as a pioneer who took that leap early. What's your immediate reaction to this news? I was surprised to hear that there were three deaths.

22:16 I will say, when I did this trial, and I remember talking with you about it on any advice I have, would I recommend doing this? I was aware that there was a death prior to me doing this. And so I really did have to take that into large consideration when I did this. Now that I'm hearing that there have been three deaths, it worries me. It worries me for people who are going to those trials that haven't been paused for a while and they're continuing to do it. I really hope that everyone is aware of these risks and that they make sure that they're making the best choice for them and weigh the benefits over the risks because the risks are there.

23:04 As you can see, we're aware of three deaths. As these safety signals have emerged, has that changed any of your ongoing monitoring protocols? No, I'm still getting monitored every three months. And I was talking with my oncologist who was managing all of this. They're getting ready to start phase two of this trial. In the MS community, CAR-T has been viewed and discussed with enormous hope, almost as a potential reset button. What's it like to balance your own personal journey and progress with the reality that this therapy also carries, as you pointed out, severe, sometimes life-threatening risks?

23:53 It's scary. We just heard about this news within the last couple of weeks. And had you asked me a month ago, Jan? We could do another round of CAR-T, would you do it? I would have jumped in and said, yes, let's do one more. Let's see if it really, can completely reset everything that's going on. But now hearing these risks, it does give me pause. And I really would have to have some really good in-depth conversations with my doctors, trying to understand what happened, what went wrong that caused these three people to pass away.

24:39 Was it a diagnosis that hadn't been uncovered or what was it that went wrong? I really would want to understand why they had those three deaths before I would take this journey again. So I think you've actually already started to answer this question. But when someone who's been newly diagnosed with MS or someone who's living with a particularly aggressive MS disease course reaches out to you and asks whether they should try CAR T cell therapy, what would be your advice today? My advice would be for them to make sure that they're aware of the risks, which can include death and has been death.

25:24 We're not just saying that it may happen. We have found that death has been a side effect of this treatment. I really would suggest that people talk with their family to make sure that everyone is aware that there are risks. We have seen what these risks have caused other people. I would make sure that they talk with their doctor. Have they tried all of the disease modifying therapies out there before they take this journey? Because really, this is a trial and we don't know what's going to happen. And I would just want to make sure that they're aware that risk could happen. And I think that they need to make sure that their family, their caregivers, their partners, that all of them are aware and that they're willing to take that journey with them.

26:11 Because not only is it just death, but you could actually have brain damage, lifelong brain damage. And is your partner willing to take on that risk and be there for you if that should happen? So I think it definitely needs to be a joint decision with the caregiver, the family members, and their providers. I am very happy to hear that this conversation, in terms of your progress, has been so positive. It sounds like you're living life at a different level than you were pre-CAR T cell therapy. And that thrills me to no end. I want to thank you so much for talking with me today.

26:55 And I hope we can connect again for a year two update. I hope so. Yes, I'm really excited to do that. I will just add one more thing about the CAR-T. So initially, we had to do a spinal tap. And mine showed oligoclonal bands. They did that spinal tap again at three months. I don't remember how many bands that I had, but my oligoclonal bands were unchanged. They made it an option at the year mark to do the spinal tap again, and I went ahead and did it. And again, there were no changes in those oligoclonal bands. So I found that to be interesting. Maybe some of your listeners might be able to chime in as to what their thoughts are on that.

27:42 If they thought maybe the oligoclonal bands would remain the same or decrease, I'm not sure, but I think that's a good question for us to think about as we move forward. Thank you for giving us one more thing to think about, Jan. Always great talking to you. Nice talking with you. Thank you so much. That's going to wrap up this episode of real talk ms real talk ms is powered by the national ms society and you can share this episode of the podcast by letting your friends or family members know that all they have to do is point their web browser at realtalkms.com slash 477 you'll find that link in today's show notes so you can easily copy and paste it right into an email or a text I also want to invite you to download the free Real Talk MS app for your iOS or Android smartphone or tablet.

28:39 The app will automatically download the latest episode of Real Talk MS. You'll be able to download and listen to past episodes. You'll be able to save your favorite episodes. And what I'm particularly excited about is that I'll be able to share all kinds of bonus content with you. And that content will only be available on the app. So I hope you'll take a minute to visit the Apple App Store or the Google Play Store and download the free RealTalk MS app. You'll find those links in today's show notes. The joint meeting of the America's Committee for Treatment and Research in MS and the European Committee for Treatment and Research in MS begins this week at MS Toronto 2026.

29:23 Next week on RealTalk MS, some of the top MS experts in the world will be joining me to talk about the latest research being presented at this meeting, and they'll explain how these discoveries are going to impact your care and treatment. I hope you're planning to join me for what are always the most listened to RealTalk MS episodes of the year. I'm Jon Strum. Thanks for listening. Stay safe and make healthy choices.