'It's all gone': CAR-T therapy forces autoimmune diseases into remission(nature.com)
nature.com
'It's all gone': CAR-T therapy forces autoimmune diseases into remission
https://www.nature.com/articles/d41586-023-03968-6
33 comments
This is quite possibly due to most of these patients already receiving DNA-damaging chemo before CAR-T therapy. It also represents only 20 cases out of tens of thousands of doses.
myasthenia gravis patients already get chemo therapy to destroy their immune cells as part of the infusion protocols. That is a treatment and is not curative. If CAR-T works on MG, then it’s not the chemo that’s doing it.
> CAR-T therapy can have severe side effects, and recipients must first undergo intensive chemotherapy that kills off many of their existing immune cells.
Damn, that really seems like a last resort.
Damn, that really seems like a last resort.
I have MS. I'm in my mid-40s and have few day-to-day symptoms. I'm fairly lucky so far.
But that could all change tomorrow. Some years ago, I woke up and couldn't see out of my right eye. It got better, but it took months to heal (and I was kind of lucky with that, too). I still have reduced grip strength from a 'flare' a few years back. What next? All it takes is one flare to make my life more difficult forever.
The current medicines tend to reduce disease activity - which means most folks have less disability and more mobility than in previous decades - and all have some side effects, which vary in intensity. At least there are pills now: The older drugs were injected at home and tended to make folks feel even worse than modern drugs.
Last resort? Not really. It might be worth the risk of chemo just to not have to have this sort of uncertainty every day. I know chemo brings its own risks, but at least there is a more clear path on what might happen.
But that could all change tomorrow. Some years ago, I woke up and couldn't see out of my right eye. It got better, but it took months to heal (and I was kind of lucky with that, too). I still have reduced grip strength from a 'flare' a few years back. What next? All it takes is one flare to make my life more difficult forever.
The current medicines tend to reduce disease activity - which means most folks have less disability and more mobility than in previous decades - and all have some side effects, which vary in intensity. At least there are pills now: The older drugs were injected at home and tended to make folks feel even worse than modern drugs.
Last resort? Not really. It might be worth the risk of chemo just to not have to have this sort of uncertainty every day. I know chemo brings its own risks, but at least there is a more clear path on what might happen.
I was recently diagnosed with MS myself and put on some of the stronger medication from what I understand (Ocrevus) to make sure my future flares will not happen or at least be a less severe.
Was the vision loss from one eye really all that sudden for you? I am noticing my left seems to feel different and act slightly different when I'm tired. For now I am assuming that eventually I might also lose this eye because of the disease.
Wish you all the best
Was the vision loss from one eye really all that sudden for you? I am noticing my left seems to feel different and act slightly different when I'm tired. For now I am assuming that eventually I might also lose this eye because of the disease.
Wish you all the best
For me, it was! But honestly, it could have been weird before and I just didn't notice. I was in the shower and realized that I couldn't see my armpit to shave it. It did get better, though: I went to a specialist eye doctor when I started my medicine (gilenya) and he said it healed really well - he really couldn't tell there was ever an issue.
If it makes you feel better, a lot of folks that do get optic neuritis find that the regain at least some of the vision. And realistically, once I got used to everything being blurry in one eye, it was probably something I could live with if I absolutely have to. Definitely bring it up to your neuro, though, just to let them know. If it is a new symptom for you, you might call sooner rather than later.
And they were right about the meds, and I appreciate the approach. Fewer flares and less severe flares mean a better quality of life for us.
If it makes you feel better, a lot of folks that do get optic neuritis find that the regain at least some of the vision. And realistically, once I got used to everything being blurry in one eye, it was probably something I could live with if I absolutely have to. Definitely bring it up to your neuro, though, just to let them know. If it is a new symptom for you, you might call sooner rather than later.
And they were right about the meds, and I appreciate the approach. Fewer flares and less severe flares mean a better quality of life for us.
I did tell my MS nurse (idk if that is a thing outside of the NL) she did seem to write it off. I do keep bringing it up everytime but it is a lot better than before. I had like a couple of weeks where I could barely look at a monitor without struggling to read anything. I'll just keep mentioning it during every checkup I will have.
I did read about the ON recovery for most so that does bring me some comfort but it still is a spooky thought.
Appreciate your reply :)
I did read about the ON recovery for most so that does bring me some comfort but it still is a spooky thought.
Appreciate your reply :)
After having seen what various auto immune diseases can do to people, I would easily take a 5-10% risk of death for a cure.
I understand that is similar to any chemotherapy no? But your body will rebuild it after ˜30days.
Chemotherapy typically isn't churn-and-burn to that extent, no.
I got CAR T-cell therapy after one complete line and a partial line of chemotherapy for Primary Mediastinal B-Cell Lymphoma, a form of Diffuse Large B-Cell Lymphoma. My first line was DA-EPOCH-R, where DA means Dose-Adjusted and EPOCH-R is one letter for each of the specific drugs involved. The drugs are given in multiple 24-hour doses over five days with multiple weeks in between, in a 21- to 28-day cycle. This lasts months, for a total of eight cycles or so.
I got an abbreviated second line of R-GemOx, which is three drugs, one of which is oxaliplatin which is, as a platin, substantially more toxic than other chemotherapy agents. That's given over the course of two days for a few hours each day, typically in an infusion center in the hospital as opposed to a hospital bed, with two weeks in between doses.
The point is, there's plenty of time and blood tests between rounds of normal chemotherapy. The point isn't to keep you low, it's to bring you low and let you recover for a bit before cycling you through again. They even give colony-stimulating factors, such as Neupogen and Neulasta, to stimulate cell production between rounds, and they give Claritin to prevent the bone pain you might otherwise get from those drugs causing your bone marrow to swell.
(The oncologist at MD Anderson was slightly horrified I was even getting R-GemOx and moved me immediately to either CAR T-cell or stem cell transplant; due to an unpromising PET/CT scan I got CAR T-cell therapy. So, no, it isn't last-ditch, but it wasn't first-line when I was sick, at least at the hospital I initially went to. However, the thinking on that might be changing. [1] [2])
Anyway, prior to the CAR T-cell infusion, I got three days of back-to-back-to-back high-dose chemotherapy specifically to destroy my immune system. It was the same drugs, not different drugs in a regimen, and by day three I was definitely feeling it worse than I ever did with DA-EPOCH-R but not as bad as my first round with oxaliplatin, which is the devil and has come to do the devil's work. The damn drug makes cold things feel like they've grown spikes, for crying out loud. How is that even possible?
[1] https://ashpublications.org/blood/article/140/Supplement%201...
[2] https://www.mdanderson.org/newsroom/car-t-cell-therapy-effec...
I got CAR T-cell therapy after one complete line and a partial line of chemotherapy for Primary Mediastinal B-Cell Lymphoma, a form of Diffuse Large B-Cell Lymphoma. My first line was DA-EPOCH-R, where DA means Dose-Adjusted and EPOCH-R is one letter for each of the specific drugs involved. The drugs are given in multiple 24-hour doses over five days with multiple weeks in between, in a 21- to 28-day cycle. This lasts months, for a total of eight cycles or so.
I got an abbreviated second line of R-GemOx, which is three drugs, one of which is oxaliplatin which is, as a platin, substantially more toxic than other chemotherapy agents. That's given over the course of two days for a few hours each day, typically in an infusion center in the hospital as opposed to a hospital bed, with two weeks in between doses.
The point is, there's plenty of time and blood tests between rounds of normal chemotherapy. The point isn't to keep you low, it's to bring you low and let you recover for a bit before cycling you through again. They even give colony-stimulating factors, such as Neupogen and Neulasta, to stimulate cell production between rounds, and they give Claritin to prevent the bone pain you might otherwise get from those drugs causing your bone marrow to swell.
(The oncologist at MD Anderson was slightly horrified I was even getting R-GemOx and moved me immediately to either CAR T-cell or stem cell transplant; due to an unpromising PET/CT scan I got CAR T-cell therapy. So, no, it isn't last-ditch, but it wasn't first-line when I was sick, at least at the hospital I initially went to. However, the thinking on that might be changing. [1] [2])
Anyway, prior to the CAR T-cell infusion, I got three days of back-to-back-to-back high-dose chemotherapy specifically to destroy my immune system. It was the same drugs, not different drugs in a regimen, and by day three I was definitely feeling it worse than I ever did with DA-EPOCH-R but not as bad as my first round with oxaliplatin, which is the devil and has come to do the devil's work. The damn drug makes cold things feel like they've grown spikes, for crying out loud. How is that even possible?
[1] https://ashpublications.org/blood/article/140/Supplement%201...
[2] https://www.mdanderson.org/newsroom/car-t-cell-therapy-effec...
When the last round of chemo is given to "destroy your immune system" doesn't it take like 2 weeks to see any signs of immune cells? I knew someone who passed away from leukemia last year because the various infections they contracted in that 2 week window caused irreparable lung damage.
Thanks for the detailed reply MSLA, and thanks for advanced medicine for you to be still with us!
I am glad you are still with us to tell us your story. Thanks.
> that really seems like a last resort
Have we had a compelling reason to research drugs whose primary purpose is to kill bone marrow in healthy patients before?
Have we had a compelling reason to research drugs whose primary purpose is to kill bone marrow in healthy patients before?
Several forms of immune system cancer treatment involve nuking the immune system and getting a bone marrow transplant from a healthy donor.
Leukemia for sure, and I think also a few kinds (or at least stages) of lymphoma.
Leukemia for sure, and I think also a few kinds (or at least stages) of lymphoma.
Sure we have, melphalan is being used to treat multiple myeloma for decades now.
Kill all the cancer in your bone marrow and transplant new stem cells to regrow it.
Kill all the cancer in your bone marrow and transplant new stem cells to regrow it.
chemo is well known for the treatment being worse than the disease...in the short term. when it works, the long term effect is well worth it.
Yeah, I wouldn't undergo chemo for something like eczema or a simple food intolerance, but if it were something like lupus or Guillain-Barré syndrome I would seriously consider it.
This depends on the chemo dose. Curative chemo doses are worse in the short term. But palliative chemo usually improves quality of life.
I mean, it varies. I got curative (or, what was intended to be curative) doses of chemotherapy for my cancer, and I felt a bit worse after the first round (which is often intentionally harsh so the oncologist can dial it in afterwords) but as my cancer burden shrank I began to feel better and better. Getting more use of my left lung, which had been crushed by a mass the chemotherapy shrank, definitely helped. But I didn't get nausea from my first-line chemotherapy, either, which likely means I'm some form of genetic freak anyway.
As a carrier of another autoimmune disease, I will be tempted to flip that switch should it become available. Since I participate in pretty much all studies they offer me, I would consider joining that one too. It might be the last one they'd ask me in for!
On the other hand, the disease is not debilitating for me. I'll also consider waiting and let a few fellow diabetics try first :-)
On the other hand, the disease is not debilitating for me. I'll also consider waiting and let a few fellow diabetics try first :-)
I have a young (30ish) friend with Rheumatoid Arthritis -luckily she doesn’t have many symptoms yet. I really really hope genetic therapy would bring a better quality of life in 10 or 20 years.
This seems unsurprising?
CAR-T is engineered to kill of CD19 expressing immune cells.
I’m sure you could take b-cell depleting antibodies as well and have it push your autoimmune disease into remission. And they are already used to treat autoimmune diseases like MS, Crohn’s, etc.
But depleting immune cells comes with a host of side effects. Risk of infection, even diseases that you’d otherwise easily fight off.
CAR-T is engineered to kill of CD19 expressing immune cells.
I’m sure you could take b-cell depleting antibodies as well and have it push your autoimmune disease into remission. And they are already used to treat autoimmune diseases like MS, Crohn’s, etc.
But depleting immune cells comes with a host of side effects. Risk of infection, even diseases that you’d otherwise easily fight off.
> But depleting immune cells comes with a host of side effects. Risk of infection, even diseases that you’d otherwise easily fight off
Some people with autoimmune disorders have to take immunosuppressors so they already have that risk of infection.
Some people with autoimmune disorders have to take immunosuppressors so they already have that risk of infection.
You could call the b-cell strategy CAR-T B (sorry for the terrible pun)
Still seems new and with relatively low sample sizes (although hard to be sure since it sounds like it's been more widely used than the work described in this paper), but potentially very exciting, especially since it seems to be pretty broadly applicable to a large number of auto-immune disorders.
What about leukemias?
A good friend of mine was cured (knock on wood) of leukemia by CAR-T. She was one of the first people to get it during a clinical trial. She'd been through all the regular chemo, bone marrow transplant, etc as well as 3 other (failed) experimental treatments and was nearly beyond hope. It seems pretty certain that CAR-T saved her life. I went hiking with her not too long ago. Pretty amazing.
That's awesome to hear! Love hearing good news like this
B-cell Acute Lymphoblastic Lymphoma (B-ALL) was the first application of CAR-T.
https://www.drugs.com/fda/fda-investigating-serious-risk-t-c...