Tackling Challenges in CAR-T Fertility Research

John Ligon, MD

Currently, little is known about the impact, if any, of chimeric antigen receptor T-cell (CAR-T) therapy on fertility. As such, more research is needed.

John Ligon, MD, an assistant professor in the department of pediatrics at the University of Florida College of Medicine, is interested in determining how best to go about conducting this research. After he presented on the topic of CAR-T and fertility at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024, CGTLive® sat down with Ligon to learn more about the ideal roadmap for further research in this field.

CGTLive: What would you say is the big picture takeaway from your presentation on CAR-T and fertility?

John Ligon, MD: I think the big picture takeaway is really that I think we need to recognize that we've been treating patients with cellular therapy for over 10 years now and we need to start thinking about these late effects. One of the most important pieces really is fertility.

I think there really are 4 different kinds of priorities that I would emphasize for us going forward. The first is that we need to have increasing collaboration amongst the different stakeholders—that includes cellular therapy providers, but also OB/GYN providers, urology providers, people interested in reproductive endocrinology, patient advocates, patients themselves—and [we] really need to come up with what the important research questions are for us to answer and how we tackle these questions. The second pieceI think is that we need to be doing a better job of educating providers so they recognize that this is a concern for their patients. At a very minimum, we should be having that conversation with patients when they are referred for CAR T-cell therapy about fertility outcomes: what we do know and what we don't know and talking about whether or not patients would be interested in referral for fertility preservation procedures. The third piece is that we need to collectively try to obtain prospective data on fertility and pregnancy outcomes for patients who are getting cellular therapy. Whether this is something that academic centers lead or if it could be done through a patient-facing registry, I think that is something that we really need to do moving forward. And then finally, I think our eventual goal is to come up with some sort of evidence-based guidelines for how to monitor fertility and who we should be referring for fertility preservation. I think that in order to do that, we really need to have that prospective data, but we should start thinking about what such a guideline would look like. That way, we can make sure that we can collect the data that will answer the questions that will allow us to write those guidelines in an evidence-based fashion.

What are some of the big challenges in this field right now?

I think that there are a couple of challenges. One is that I think many cell therapy providers still don't recognize that this is an important priority moving forward. This has traditionally been a treatment that has been given to relapsed and refractory patients who have already seen multiple lines of therapy and so their fertility may already have been impacted. This won't necessarily be the case as cellular therapy moves forward. The other major piece is that because we are standing at the very beginning of trying to answer these questions and we have so little preliminary data, it is challenging, honestly, to get funding to start answering some of these questions. I think that we really need to, again, increase collaboration, try and do some pilot studies, and begin to start answering these questions so that we can get funding to do larger studies.

Is there anything else you want to share?

I think that this is a really exciting time for cellular therapy. I got to talk about in my presentation that we're now seeing CAR babies: The patients who have gotten CAR T-cells are now cured of their disease and they're going on and having families of their own. These are the kinds of outcomes that I think really give our patients hope. It's important, I think, for us to start trying to collect data so that way we'll be able to better answer our patients’ questions when they come in and ask what life is going to be like after they get CAR T-cells.

This transcript has been edited for clarity.

Click here for more coverage of Tandem 2024.

REFERENCES
1. Ligon JA. CAR T-cells and fertility. Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas.