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.
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.
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?
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).
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.