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Comment by KaiserPro | Hacker News Reader

the grade 3/4 cytokine release syndrome is a bit of a worry. But then how different is it from normal cancer treatment?

If i'm dying of cancer i'd take the risk. Hopefully though they'll have that figured out.

Not an expert at all but I'm preparing to go through assisting someone with CAR-T therapy soon. This is just from what I've seen with their treatments and visits so far.

In the previous chemotherapy it was dosed at regular intervals and they could make adjustments to the speed of the dose, supplemental medication, and maybe dose size(?) but the close supervision was more or less right around infusion followed by 3 weeks without medical care. With the CAR-T we're looking at about a week of 8 hours every day in the clinic, followed by 3 weeks of slightly fewer days each week. In addition the caretakers (family/friends) are to monitor the patient at all other times for signs of cytokine release and the neurological effects. There are steroids used to reduce the impact of both but they need to be applied fast enough. The patient is supposed to be monitored 24/7 for a month, and for patients who live more than a hour from the clinic they have to stay in a hotel and cannot go home.

It seems more serious than the initial chemo cycle but it seems to me that part of that is because they inject the modified cells then just watch.

Yeah I had a suspicion that this might be the case for "normal" chemotherapy as well.

Thank you for this data point, and I wish your family member(forgive my assumption) the very best of luck.

Following CAR-T studies earlier from Novartis, I recall that cytokine release as an adverse event was also highly predictive of the treatment's efficacy. So terrible as it is, it's also an indication of the immune system at work.

One difference would be that you can stop any treatment in case of adverse events. But you can’t remove CAR T cells from the body once they’re in.

I mean yeah, its about balancing risks. I'm guessing that a ~2% chance of a cascade would mean that its not likley to be given as a first like of defence.

In a lot of cases we don't have other first line options. it may be no treatment die in 6 months, standard treatment die in 10 months, or this where 2% die in 1 month but 98% are cancer free 1 year later. All numbers above made up, but those are often what we are dealing with.

Of course where we have other cancer treatments that works well those should be a first line (at least for now - who knows how this will advance), but all too often we don't have good options.

> you can’t remove CAR T cells

Well there working on blood purification in severe cases: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245117/

"Four-day extracorporeal blood purification resulted in complete resolution of immune effector cell-associated neurotoxicity syndrome and greater than 95% reduction in interleukin-6 levels without side effects"

Cytokine release syndrome was also a problem with other CAR-T treatments that they work through.

Read the long portion on cytokine syndrome with the yescarta acquisition

https://www.gilead.com/news-and-press/press-room/press-relea...

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