New FDA Warning for CAR-T

There was some bad news for CAR-T treatments issued yesterday -- the FDA called for  "Black Box Warning" for CAR-T treatments. These would include the CAR-T treatments that have been approved for Follicular Lymphoma. 

This follows reports from November that some CAR-T treatments were leading to T Cell malignancies. In other words, with the treatment that involves changing T cells to find and eliminate cancer cells, those T cells could turn cancerous themselves. 

There's a lot to unpack here, and I'm trying to be rational about it all. 

First, the FDA's action. Issuing a "Back Box Warning" means they are adding a literal black box or border to the packaging insert of the treatment. The black box is meant to make it stand out and be noticed. The warning is considered the highest safety-related warning that the FDA gives, and it usually means that the treatment can lead to severe side effects. There are currently over 400 approved treatments, including many cancer treatments, that have Black Box Warnings, and the warnings can be changed or removed over time as new data becomes available.

The FDA warning came because a large number of patients who have taken CAR-T treatments have developed T cell cancers. In the letter that the FDA sent to manufacturers of CAR-T treatments, they said that they have become aware of this risk and that the new cancers have "serious outcomes, including hospitalization and death." How many patients have developed new T cell cancers? I can't find a definitive number, but it may be as high as 22. That doesn't seem like a lot compared to the thousands who have received treatment, but it's enough to issue the warning, especially since they develop over time. Doctors have been asked to be especially vigilant with CAR-T patients and continue to monitor them, even after they have been in remission for some time. 

The call for the Black Box warning isn't complete. The manufacturers have 30 days to respond to the FDA, with changes they will add to the labels, or a statement of why they think the label warning isn't necessary. 

So what does this mean for Follicular Lymphoma patients?

I'm not really sure. As I have said before, I'm not an oncologist or cancer researcher.

But really, I'm not sure even oncologists know at this point. It's very new, and they seem to be digesting the news (at least in the conversations I am seeing online).

Any new Black Box warning makes doctors take notice, obviously. They need to rethink the kind of risk/reward calculations that they always make when considering a treatment for a patient -- essentially, will this treatment create more problems than it solves? Every treatment has side effects, some more severe than others, some that affect certain patients more than others. That's not going to change. But they're going to have a lot more to think about.

Some interesting reactions online that I have read:

• This may lead some doctors to recommend CAR-T for older patients, if T cell cancers develop many years later, rather than younger patients who will be at greater risk.
• This may lead researchers to create "kill switches" on the T cells, so if they turn malignant, they can be more easily killed off (don't know if that's even possible).
• There is still a lack of data over the relationship between CAR-T and the new cancers. In other words, researchers are still looking to see if the T cells that were changed as part of the treatment are even the same T cells that turned cancerous. That's extremely important data to have. 
  
• At least one oncologist who I respect a lot says CAR-T will still be a great help to many of his patients, and that the new cancer is "low risk."
• Another said the rewards of CAR-T far outweigh the risks, especially since CAR-T is often used now for patients with "dire prognosis."

So as I said, I'm trying to be rational about it all. In my own case, CAR-T isn't something that my oncologist and I have discussed for me right now. Maybe that changes over time. And maybe by then, there's more data about this issue to help make a decision.

So, the same advice applies as always. Have an oncologist that you trust, and have honest conversations about treatment -- your goals, your fears, and your needs. Then make the best decision you can.