[doctoring]

Wow, I am so sorry. Thank you for sharing part of Melanie's story.

Your thought about the drugs maybe limiting the effect of the CAR-T is an interesting one and the subject of ongoing investigation. One common drug used for CAR-T related cytokine release syndrome, tocilizumab, does not appear to have negative effects on CAR-T proliferation or efficacy. However, it doesn't seem to do as much for neurotoxicity (which seems to be a separate mechanism from the cytokine system), and they often have to resort to steroids for that. Steroids do dampen T-cell activity, but to what degree that impacts CAR-T effectiveness is not clear. However, as you mention, sometimes you are left without much choice.

[mft_]

> Steroids do dampen T-cell activity, but to what degree that impacts CAR-T effectiveness is not clear.

It's an interesting question. Tangential, but in the early days of discussing how to incorporate anti-PD1s into different treatments, there was lots of concern about the negative effects of steroids --let alone chemo-- on T-cell function. Yet a few years later, aPD1 + chemo is well established in lots of settings.

And likewise, despite data from mouse models that steroids and chemo do impair T-cell function, we're now seeing CAR-Ts and also CD3-engaging bispecific Abs combined directly with chemo - again, with good efficacy.