Thread by @VPrasadMDMPH

Few prelim thoughts on this trial (from quick read)
#ASH21
1. It is not a 'second line' trial, it is a trial in the worst subset of second line pts & cannot extrapolate beyond

Primary refractory & relapse <12 mo

(TBH, a lot of people doing this already)

As such, it should not generalize to relapse > 12 months

2. That said, for those included, axi-cel seems preferable to chemo then auto; I am not surprised this is true in the most chemo insensitive biology. But a few more thoughts

3. This is Wrong, you are not supposed to do this 👇👇
Standard practice is to take these pts to CAR-T if needed in the control arm; thus, you must compare routine, upfront CAR-T to using CAR-T as salvage when indicated and standard of care.

And you don't adjust for it

You want to prove that routine, upfront CAR T is superior to salvage CAR-T

That's literally the Q: one of sequence.

Control arm attrition is terrible, which tells you this is the worst of the worst DLBCL (and the trial does not extrapolate to all second line)

This is a silly way to show the data.
Better to break the <12 month relapse into 1-3, 3-6, 6-9, and 9 - 12.

The idea would be that as relapse occurs later, auto remains superior

Even with the deck stacked in favor of axi-cel

Would be less impressive with indication drift & better use of CAR-T post protocol for control arm

Overall: ok study, but not really as impactful as I had thought.

The population is a narrow one and very chemo-insensitive. This supports CAR-T second line for such pts, as many were already doing.

Worry: there will be indication drift to all second line

I also like this 👇