Relapsed cancer patients die so asymptomatic pre-cancer patients can go on trial
Is this tradeoff really so bleak?
It is official, Dana Farber investigators are testing CAR-T in patients with pre-cancer. In other words, a very toxic drug product is given to people who have an asymptomatic, pre-cancer.
I have criticized the enthusiasm to treat smoldering myeloma b/c we still lack good evidence that treating is better than observing. Famously the ECOG investigators confounded their own trial, which will prevent a reliable answer. The Spanish trial is an underpowered study, whose OS is unreliable, and occurs in the setting of poor PET and poor post protocol therapy. With Aaron Goodman and Sunny Kim, we made the argument against treating here.
With Manni Mohyuddin, we pointed out just how many of the ongoing studies are non-randomized. Non-randomized smoldering myeloma studies are practically useless. Of course, giving drugs that we give sick myeloma patients can be given to healthier smoldering patients, but are they better off? Only trials with a control arm can tell us.
Enter the latest dilemma. Drug companies have been stingy with CAR-T slots, and many of us have had difficulty making referrals or getting product, facing long lists. Now they are taking that precious manufacturing capacity and using it for uncontrolled smoldering studies. As Samer Al Hadid says
![Twitter avatar for @HadidiSamer](https://substackcdn.com/image/twitter_name/w_96/HadidiSamer.jpg)
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Is he right? Are companies letting sick cancer patients die without CAR-T to run trials in less sick patients?
I am afraid he is. Obviously the company is seeking a broader market share and that trumps their desire to offer the product to those who have no options. But we cannot blame the tiger (pharma) for being the tiger. The failure is regulators who permit useless trials (all uncontrolled studies in premalignant conditions where standard of care is observation are useless).
Companies chase their incentives. They can’t be faulted for that. We have to ask why the rest of us don’t push back. They may be the tiger, but why are we toothless.
PS: I heard some Plenary Session listener say I love BITEs and hate CARs. That is untrue. I like that BITEs are off the shelf, but hate the infections. I love that CARs are one time, but hate the manufacturing failure. I hate both their prices. I don’t do any work with drug companies. I have no financial bias here— just opinions.
Vinay, I’d be interested on your take at some point on pharma’s push for coverage of expensive somatic gene therapies to treat sickle cell disease vs the relative lack of insurance coverage/funding for IVF/PGT which would prevent most cases of SCD to begin with.