More Research is Needed to Provide Patients With Guidance on CAR-T Late Effects

Currently, not much is known about long-term safety risks of treatment with chimeric antigen receptor T-cell (CAR-T) therapy. Although research into this is underway, it is complicated by the fact that CAR-T is a relatively new modality that has only become commonplace in the past few years, and the fact that many patients receiving CAR-T have been pretreated with multiple other drugs or therapies known to cause late effects.

Aimee C. Talleur, MD, a physician at St. Jude Children’s Research Hospital, gave a talk on this topic entitled “CAR T-cells and late-effects, including secondary malignancies” at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024. In an interview with CGTLive® at the conference, Talleur emphasized the need to do more research so that physicians can provide patients and their families with proper guidance on what to expect after receiving CAR-T.

CGTLive: What was the rationale behind your talk on late effects from CAR-T?

Aimee C. Talleur, MD: We know that survivors of pediatric cancer are definitely at risk of a lot of late effects related to their prior treatments. With CAR T-cell therapy that's relatively new, with the first child being infused with CAR T-cells in 2012. As such, we don't really know what a lot of the late effects specifically from CAR T-cell therapy may be so we're really looking to better understand that and develop prospective studies.

Can you give an overview of the main points you discussed during your presentation?

Really the goal of what we're trying to do is come together as a community and really develop multiinstitutional efforts so that we can learn as much as we can from every patient that's come through CAR T-cell therapy and really help to develop better guidelines on how to monitor patients afterwards. We really [want to] work together to develop these prospective efforts to study these patients and help them as much as we can.

Could you summarize the big picture implications you would want doctors and the broader healthcare community to take away from your talk?

I think there's been a lot of research over the years and over the decades to better understand late effects after cancer therapy. From that work we've been able to better guide our survivors on what care they need to get and what testing they may need to follow up on with their primary doctor to better monitor for these late effects. With this new population of patients that are treated with these novel therapies like CAR T-cells, we don't have that for them. Ideally, what will be able to come out from this will be [the ability] to give better guidelines and better information for our patients and families so that they can better care for themselves.

What are the major challenges in this space right now?

A big challenge with studying late effects after CAR T-cell therapy is that right now, most patients that are treated with CAR T-cells are heavily pretreated, meaning that they've undergone many rounds of therapy; potentially a stem cell transplant, radiation, lots of chemotherapy, etc. All of those things have their own late effect risk profile so when we're starting to study this patient population, trying to understand what might be directly related to the CAR T-cells versus what was maybe added on to their already-existing risk profile of late effects because they're a cancer survivor, will be very difficult to tease out. But our goal as we study more patients, and we get a better grasp on this, is that we will be able to see some of those signals that might inform on our future guidelines.

Is there anything else you would like to share?

I think an important aspect of these kinds of efforts is really the involvement of patients and families and advocates. We really want to understand not only what is important to us as medical providers, but also what's important to them. What are they worried about? What questions can we help answer? As these efforts are being developed and as we're going through things, it's going to be critical that we really involve these patients and the families so that we can do the best job for them and for us.

This transcript has been edited for clarity.

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REFERENCES
1. Talleur AC. CAR T-cells and late-effects, including secondary malignancies. Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas.