A Follow-Up on Secondary Cancers and CAR-T

 A follow-up to the news from a few months ago that the FDA was issuing a warning about CAR-T causing secondary cancers. After reports of patients who had received CAR-T developing T cell cancers, the warning was issued in January. 

The concern was that the patients were developing T cell cancers specifically. CAR-T, of course, currently made for each individual patient who receives the treatment. T cells are removed from the patient, manipulated to recognize cancer cells, and put back into the patient. Because the T cells are manipulated, the concern is that the process might go wrong in some way and make the cells cancerous. There are several varieties of CAR-T (it's a general category, not a specific treatment, though I know I often write about it as if it is one thing and not many). Each one has a slightly different way of manipulating the cells. But they do have the same general process.

Since then, there has been some research on just how common secondary cancers are among CAR-T patients. This morning, the journal Blood published "Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS)." I can't see the article, or even a summary, but ASH, which publishes Blood, put out a press release about it, which is very helpful.

The researchers who wrote the article looked at the FDA's Adverse Events Reporting System, or FAERS, and catalogued the number of times CAR-T patients reported developing a new cancer. The FAERS system is voluntary -- an adverse event, or side effect, can be reported by a doctor, or a patient, or by someone else. So it's possible that some of the adverse events were reported more than once, by both a  doctor and a patient. And it's very possible that an adverse event wasn't reported at all.  So it's important to keep in mind that these numbers are not comprehensive.

That said, they do offer at least a small picture of how common secondary cancers are in CAR-T patients.

The researchers looked at a total of 12,394 adverse events that were reported about CAR-T patients. They found that 536, or about 4.3% of the adverse events reported were secondary cancers. So, to be clear about this -- of all of the adverse events (or side effects) reported voluntarily, 4.3% were new cancers. And to be even more clear -- there isn't necessarily a clear connection between the treatment and the new cancer. It's certainly possible, but not definite.

I'll give you an example of how this works. I received Rituxan 14 years ago. I was diagnosed with a secondary cancer (a skin cancer) a few months ago. Did the Rituxan cause the cancer? Maybe. Did my immune system cancer cause it? Maybe. Did my never wearing sunscreen as a kid cause it? Maybe. Was it a combination of al three? Maybe.

It's really difficult to connect a secondary cancer to a previous cancer treatment. But there can be a comparison to other populations who didn't get cancer treatment, and compare how common the cancers were.

So which cancers were most common among CAR-T patients? Leukemia was most common -- 2.7% of all of those 12,394 adverse events were leukemia. Skin cancers (the most common secondary cancers among all cancer patients) were 0.4% of the adverse events.

And T cell cancers, the type that are most concerning? They amounted to just 0.1% of all of the adverse events reported. 

I want to be clear here -- I'm not saying here's no danger of getting a T cell cancer. The fact is, I don't know. And I can't say for sure what the odds are of getting any secondary cancer. The FAERS system only gives a partial picture of things. 

I'm not an oncologist or a cancer researcher. If you're concerned about secondary cancers -- if you're concerned about any adverse events or side effects -- the best person to talk to about it is your own oncologist. They'll have a much better idea of what the risks and rewards are for any treatment you might have.

And that should be a part of any conversation you have about treatment, anyway, whether you are in need of one immediately, or you're thinking about the future and what might happen when you do need treatment. It's easy to trust your doctor when they have a suggestion for treatment (and I hope you have a relationship with your oncologist that does allow you to trust them). But make sure you know everything you can before you make that decision together.