[apathy]

Not mentioned here: the same results can in many cases be had from BiTEs at lower cost and without having to ship leukapheresis samples to the US in liquid nitrogen

Having seen both ALL and AML patients relapsing through CAR-T, I don’t think people appreciate either the systemic load or the possibility of treatment failure that exists in real patient populations. Neither was elderly; 26yo female ALL and 5yo female AML. Both dead, both crushing disappointments after the initial excitement.

(For CAR-T therapy, the common remark is “you know it’s working when the patient goes to the ICU” from tumor lysis; but in both cases the patient’s disease outran their engineered T cells)

[dannykwells]

It's not really fair to compare BiTEs to first gen CAR. Bispecific (or tri/quad specific) CAR have a greatly reduced rate of relapse due to antigen loss (likely what is causing most relapse in these diseases).

Re: BiTEs, it's not clear they'll produce durable cures like CAR does. They're just antibodies, and will eventually be cleared. With CAR, if you can get a response, you can generate memory T-cells and control any relapse far down the road.

[apathy]

At least for lineage switching malignancies (5yo female was MLLr), I’m not sure anything other than synthetic lethal attacks on the clonal driver will help.

MLL rearrangements in young children have a particularly vile habit of swapping cell surface markers wholesale. They’re almost certainly more potent when they transform fetal liver progenitors, which seem to retain maximum plasticity. AA died prior to the introduction of second and third generation CAR-T, but stan riddell was part of her attending team, so I have to assume all the stops were pulled out.

MG was different, 26yo Philadelphia-like ALL with 300k WBC refractory to everything. She should have been on ruxolitinib then transplanted. Her disease simply outran her T cells’ ability to divide. It was unreal. And she was a single mom.

I will never forget either case. Even as just an “attached” fellow, it’s hard to watch. More so (for me at least) than older patients where you can reasonably guess what’s coming next. It just feels so unjust.

Anyways. Let’s hope I’m wrong and 2nd/3rd gen auto and allow CAR-T can put these kinds of cases into durable remission for the rest of their, hopefully long and healthy, lives. Because right now, nothing does.

[lliamander]

Immunotherapy is really fascinating, I know someone going through it right now and it seems to be helping (early days yet, of course).

I was very curious to read that it had such severe side-effects, especially the neurotoxicity. Why such a severe reaction? Does the neurotoxicity have developmental impacts for children that receive immunotherapy?

[dannykwells]

The origin of CNS toxicity is still a topic of research. I believe it can occur in children as well (I am not an MD and specialize more in the checkpoint inhibitor side of things).

[lliamander]

> For CAR-T therapy, the common remark is “you know it’s working when the patient goes to the ICU” from tumor lysis

Why is that not also true in chemo patients?

[DrJosiah]

(note, I'm not the right type of doctor to answer this properly, but my understanding is...)

A lot of chemos are some type of poison, only slightly worse for the tumor than it is for the rest of your body. It doesn't die fast enough (and if it did, you'd be killing the rest of you too). Think months / years with chemo vs. weeks with CAR-T.

[lliamander]

Ah, so it just kills it faster?

I know a child with leukemia who recently started chemo. They had him on sodium bicarbonate and other medication to reduce the acidity of his urine (to compensate for the increased amount of uric acid). However, they only had him on it for the first few days of chemo. My understanding was that the bulk of the chemolysis occured in that period (though I could be mistaken).

[DrJosiah]

It kills specifically. The immune therapies are turning your (or someone else's) body's T cells into murder machines, tuned specifically for a target. And because it is so good at its job, cleaning out the biological waste from destroying cancer is difficult, so trips to the ICU are not uncommon.

Chemo kills everything in your body, just the cancer a little bit more. You do the chemo, wait a few weeks, then do chemo again, wait a few weeks, maybe get a scan, do chemo again, wait a few weeks, ..., maybe in 6 months if your treatments are going well you keep going, maybe they switch you to something else, maybe this round is done and you take a break for a while. You wait because if you don't, the poison kills all of you, not just the cancer.