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
Here's what they are not saying
Vaccine hesitancy has been rising for some time. This includes preventable illnesses like measles. There will be measles outbreaks in the future! Covid policy accelerated hesitancy. The question is: how many extra outbreaks will occur bc of RFK...
... If RFK is HHS secretary, versus if RFK is not HHS secretary. That's the question.
Even though he has tremendous administrative authority, he has already stated he's not going to withdraw these vaccines. I also suspect it's not going to be the first topic he touches...
Moreover, I and others have repeatedly provided compromised positions where we can improve safety detection of current vaccines. The current system can be honest and admit that our vaccine surveillance is abysmal. Companies don't want safety discovered.
Every single one of these garbage papers use the denominator of PCR+ covid infections, and not the actual denominator of people who had covid-- many do not present to the doc. Every single one of these papers is shit. I would be embarrassed to be an author. Incompetent work.
People with covid who are so sick they have to go to the doctor have poorer health than people who don't. That should be in the journal of obvious things. All of these authors are extrapolating beyond the evidence. They're creating a body of trash calling itself science
Is there a single paper that uses a sero prevalence denominator? Is there a single researcher in this field whose brain is working? Just one. That's all I ask for.
Totally wrong. Because Vincent is not thinking about the counterfactual correctly.
*Teachable moment*
1 These drugs were approved by accelerated approval in the LAST line. Some later improved survival & others didn't in an EARLIER line.
2 The counterfactual to AA... 🧵
is demanding RCTs powered for say, OS (survival). If a company couldn't use RR to get AA, they wouldn't run a trial in the 2nd line or 3rd line setting powered for OS, they would run it in the 7th or 8th line
Why? more dire = faster result
3. We have proven that in these v late lines RR and median DOR (the current AA criteria) result just as fast as OS pubmed.ncbi.nlm.nih.gov/30933235/
Many people want covid to be worse than it is. They imagine it has long-term consequences that are worse than other respiratory viruses. Adjusting for severity of illness, it doesn't. Only anosmia is unusual. Why do they want it to be worse than it is? 🧵
For some reason, some people want to live with perennial precautions. They don't want to take off the mask, they want their children to mask, they want to keep getting booster after booster. I don't know why but they want to live in fear.
They have...
A mountain of retrospective observational data that they think supports their claim that covid has long-term disability. That it's a vascular disease. And all sorts of other claims. Nearly all these studies are flawed. They don't have good controls.
Lots of prior studies show many psychological findings don't reproduce. Obviously that's because so much of this science is bullshit. Small sample size, weak methods. Entire fields struggling to justify their existence & people p hacking and exaggerating to be on @HiddenBrain
How do you fix this problem? No one really knows. All of academia is incentivized for hype and discovery, actually being a thoughtful student, criticizing things, pushing for better methods that's unpopular.
Thank you @Erman_Akkus for ur reply it is a good learning opportunity for #ESMO24
In 15 tweets, I will summarize the trial, my criticism, and why this reply contains 3 common errors that oncologists make because our training doesn't teach these ideas.
First, the trial...
The trial is #LEEP-012 and randomizes pts with INCURABLE (see pic) liver cancer to TACE (embolization) plus costly drugs or embolization alone.
These 2 drugs are TOXIC (lenva is horrible) and cost a FORTUNE 200-300k per annum per person
#ESMO24
Every single person has the cancer return. It is non-metastatic, as @Erman_Akkus says, but it is not curable.
Here is the time until measured lesions grow 20% or new lesions present or the patient dies
That's what he and others are excited by #ESMO24
a 4 months PFS