FDA Investigation of CAR-T

Last week, the FDA announced that it was "investigating serious risk of T cell malignancy" in patients who have received CAR-T treatment. 

Obviously, any time the FDA issues a statement like that, it's worth looking into and being concerned about. But it's also worth noting that the statement also says that the benefits of CAR-T outweigh the risks. 

The statement from the FDA points out that they have received reports of CAR-T patients developing T cell cancers. In other words, the T cells that were manipulated as part of the treatment have become cancerous. Some of those patients then had to be hospitalized or died. This is alarming. Any treatment that results in death of the patient is problematic.

I realize that I'm walking a fine line with this post. I want to look at both sides of the issue but not minimize the problems that CAR-T might be creating. I'm also trying to stay positive, keeping in line with what I see the FDA statement as doing. 

The website Fierce Pharma has a good article on the FDA statement, providing a good bit of context. They provide some good numbers about CAR-T. Maybe most relevant is the data related to Kymriah and Yescarta, the two CAR-T treatments that can be used to treat some Follicular Lymphoma patients, and are the most-used CAR-T treatments (there are six in total). 

From those six versions of CAR-T, there have been 12 reported cases of T cell cancers. (I have seen elsewhere that it might be 19 cases). Ten of those 19 came from Kymriah and Yescarta patients. In statements from both of the manufacturers of these CAR-Ts, they pointed out that they are aware of the problem and are monitoring all of their patients (there have been over 27,000 patients who have received either Kymriah or Yescarta).

Again, I want to be clear that I know I am walking a fine line. 10 cases of T cell cancer out of 27,000 isn't many. But it's the entire world to those 10 patients. Even 1 more cancer in the world is 1 too many. And 12 (or 19) is enough to get the FDA concerned that more might be coming.

I've spent a week or so trying to find more context for all of this, and it's hard to find. One really good source, though, is the podcast Tumor Talk from Dr. Wes Wilson, a cancer researcher at the University of Pennsylvania. I'm having a hard time finding a good link to Tumor Talk, but you should be able to google the podcast name and find ways to access it through Twitter/X, which is how I found it.

Dr. Wilson points out that the FDA has not imposed any restrictions on CAR-T (which happens with some FDA warnings). Dr. Wilson also points out that CAR-T patients who received the treatments had already been heavily pre-treated, and so may have had weakened immune systems and been more susceptible to cancer. CAR-T can also suppress cells that fight cancer, making patients more susceptible. All of that said, he also has not heard of any UPenn patients (there have been over 100) who have developed T cell cancers. There are also several ways that T cells are created for CAR-T treatments, and it is possible (but not yet shown) that processes that were developed before FDA approval are the ones that have caused the problems -- that is presumably part of the FDA investigation. Finally, when the treatments were approved, one of the published potential side effects is the development of secondary cancers. That's true of many cancer treatments -- certainly true of traditional chemotherapy. Secondary cancers are common, unfortunately.

The question becomes one of risk tolerance. As Dr. Wilson says, CAR-T is still more beneficial than not receiving treatment. As of now, the data shows that the risk-benefit is "strongly weighted" toward getting the treatment. And it seems that many cancer hospitals are saying the same thing. And so is the FDA.

So what do I think about all of this? 

Who cares? I'm just a patient. The best person to talk to about this is your oncologist. Every cancer treatment has side effects, and thus come with risks. What's important is being aware of the possible treatments, how effective they might be for your situation, and how the potential side effects will affect your life, given your goals (are you looking for a cure? for long-term remission? for the least aggressive treatment that lets you maintain your quality of life?). Only you and your oncologist can answer those questions. 

In the meantime, I will certainly keep looking out for more news about this. (The FDA statement doesn't give a whole lot of detail, unfortunately.) If you are unfortunately in need of treatment soon, talk to your oncologist about all of your options, including CAR-T, and decide what's best for you.