BETA - What are the risks of secondary cancers associated with CAR-T therapy?

When you're considering CAR T therapy, it's natural to focus not just on how well it works, but also on what it might mean for your future health. One important question is whether CAR T could increase the risk of developing a second cancer. In this video, we'll walk through what's known, what's still being studied, and how patients are followed long-term to keep them safe. What is the risk of secondary cancers associated with CAR T therapy? When thinking about secondary cancers in CAR T cells, the first thing to emphasize is that it's pretty rare to see secondary cancers after getting CAR T cells for multiple myeloma. And there are a few different types of secondary cancers that we think of. Some of them, when we see them, may not actually be related to the CAR T cells. Most people who are getting CAR T cells for multiple myeloma have gotten many other treatments for multiple myeloma. And several of those we know are definitely associated with a risk of second cancers later on, including the high-dose melphalan chemotherapy that we use for stem cell transplants, and even the Revlimid that's used as maintenance therapy after stem cell transplants have been shown in clinical trials to give small increases in the risk, especially of bone marrow cancers like myelodysplastic syndrome and acute leukemia. And so some of the second cancers that we see develop after subsequent myeloma therapies like CAR T cells are probably more related to earlier lines of therapy that people have gotten for their multiple myeloma. CAR T cells definitely suppress the immune system. And so we see occasional times when patients develop second cancers that we think are probably related to immune suppression, allowing especially T cell lymphomas to crop up, some of which are related to viral infections that might have more of a chance to grow after an immune suppressive therapy like CAR T cells. And then we have seen case reports of very occasional T cell cancers that are actually formed from the CAR T cells themselves. And this is because CAR T cells are manufactured by using a virus to insert a new gene into the patient's own T cells, own immune T cells. And that gene, if it got inserted in just the wrong spot and interfered with the workings of other genes in the patient's genetic material in those T cells, could conceivably turn those T cells into cancerous T cells themselves. We used to think that was primarily a theoretical concern because we essentially never saw it happen, but there now have been a few reported cases of CAR T cell related cancers themselves. It's an extraordinarily low risk and at least right now it seems to be very much outweighed by the beneficial anti-myeloma effects of the CAR T cells. Talking about the risk of second primary malignancies, it's a really complicated topic and it's really hard to isolate what's the cause of these things. I like to tell patients first and foremost that myeloma is a cancer of the immune system and our immune system plays a role in trying to prevent or limit cancers in the body that we may not even know about. So there's probably a slight increased risk of cancer just having a problem with the immune system at baseline. And recently we've also seen this signal in the studies after CAR T cell therapy. It's a little hard to tease out what is the cause of these things. What I'll say is that for CAR T at least, we see a whole spectrum of possible second primary malignancies. Most common are non-melanoma skin cancers, things like squamous cell carcinoma or basal cell carcinoma, which it's just important to see the dermatologist for these lesions. They can be removed and usually don't cause issues but do require attention. We also do see solid cancers, things like breast cancer, colon cancer, prostate cancer. So it's important even though you're being treated for myeloma to continue to see your primary care doctor, get the age appropriate cancer screenings and stay vigilant on that. But the types of second primary malignancies that really concern us most are second types of blood cancer. That is primarily MDS, which stands for myelodysplastic syndrome, which is really just an ineffective production of blood cells from the bone marrow, or AML, which is acute myeloid leukemia, which is a more aggressive variant of that. Both of those things can be very challenging to treat if they occur. Are secondary cancers being seen in other cancer types or just in CAR T therapy being used in multiple myeloma? All of those types of different cancers that we see happen after CAR T cells can be seen with any kind of CAR T cells. The immune suppression with CAR T cells used to treat leukemias and lymphomas can be just as intense as the immune suppression that we see with CAR T cells for myeloma. And the risk of causing a CAR T cell-related T cell cancer is the same regardless of which type of target the T cells are going after. And so although very rare, it has been seen with T cells targeting lots of different targets, including those used for treating other cancers. What was the prevalence of second primary cancers on the initial FDA report? With the initial study of silt to cell carvicti, about 10% of patients were later noted to develop either this MDS or AML, which was a concerning and high signal for that. However, it's important to remember that these patients had received a lot of prior treatments, including high dose melphalan with their transplant, other cytotoxic chemotherapies, and other therapies. And it's hard to know how much is the CAR T contributing to that risk. But nonetheless, it was a fairly high signal and warrants further attention and a lot of conversation with patients. When silt to cell was studied in earlier lines of therapy, that signal was much better. About 2% of the patients rather than 10 were noted to have development of MDS or AML after the fact, but still a little bit of a signal. And so I think the question really is that we'll have to evaluate in future studies, is the CAR T by itself increasing that risk of the second primary cancer? Or is it a synergy between the prior conventional chemotherapy that then the CAR T may accelerate the timeline of developing that problem? And so in the future, when we have some studies comparing upfront CAR T versus transplant, we may get a little bit more answers about that. What monitoring is used to detect secondary cancers? For patients who have gotten CAR T cells, right now our standard practice is to do standard monitoring for other cancers. That means age appropriate monitoring for breast cancer with a mammogram, for colon cancer with colonoscopy, and consideration of screening for prostate cancer just as you would if you didn't have multiple myeloma and weren't getting immune suppressive therapies. And then layered on top of that, we monitor anyway for bone marrow cancers just by doing regular blood work as part of people's regular testing for their multiple myeloma. And so there isn't really any added monitoring that you need to do for second cancers because we're already doing such a good job of watching out for cancers anyway. Is there any way to reduce the risk of secondary cancers? Well, we can start out by saying that the risk of second cancers after CAR T cells is already probably very low. And so trying to come up with a strategy for reducing that risk is going to be difficult. I think the standard monitoring that we do for cancer screening and the regular monitoring that we do anyway as part of routine follow-up for patients with myeloma is probably a big bit about as good as we can do. It's possible that we'll come up with some additional strategies, but right now there's no evidence to show that there's any other strategy that will directly affect that risk of second cancers. While the idea of a secondary cancer can feel scary, it's important to remember that this risk is rare, closely monitored, and still being actively studied. For most patients, the potential benefits of CAR T, including long-term disease control and even remission, far outweigh the known risks. Ongoing follow-up, regular check-ups, and open communication with your CARE team are key to staying healthy after treatment. Knowledge is power, and being informed helps you move forward with greater confidence and peace of mind.