Integrating Gene Therapy into Clinical Care for Sickle Cell Disease

The FDA's approval of Vertex Pharmaceuticals' and CRISPR Therapeutics’ gene editing therapy exagamglogene autotemcel (exa-cel; marketed as Casgevy) and bluebird bio’s gene addition therapy lovotibeglogene autotemcel (lovo-cel; marketed as Lyfgenia) for sickle cell disease (SCD) came in December 2023, but rollout of these therapies into the commercial treatment landscape is still ongoing. This partly comes down to the complexity of these novel treatments, for which clinical institutions need substantial infrastructure and interdisciplinary team coordination in order to delivery safely and effectively.

At the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 6 to 9, 2025, in Orlando, Florida, CGTLive® sat down with Crawford Strunk, MD, an associate staff member at the Cleveland Clinic, which is currently in the process of treating its first patient with SCD gene therapy in the commercial setting. Strunk, who is also codirector of the Sickle Cell Medical Neighborhood, explained how institutions become gene therapy authorized centers, discussed the Cleveland Clinic's experience with integrating gene therapy into its practice, and touched on how care teams discuss the decision of whether to start gene therapy with potentially eligible patients.

CGTLive: Has the Cleveland Clinic integrated gene therapy into care for patients with SCD?

Crawford Strunk, MD: At the Cleveland Clinic, we have been identified as an authorized treatment center for both Casgevy and Lyfgenia and we are working through our patients now. We've had several patients on-study go through gene therapy, but our first commercial gene therapy patient is right around 100 days at this point and is ready to go back to her primary hematologist in the next couple weeks.

What does an institution need in order to start integrating gene therapy into clinical practice?

Before you can even become a gene therapy authorized center, you have to make sure you have the capability of apheresing off the stem cells, being able to preserve them, being able to ship them appropriately, and being able to get them to the company that's going to be manufacturing the cell product. That requires a certain level of blood bank care, a certain level of apheresis care, and a certain level of of cellular therapy care, which is not available at every center in the country.

In addition, certain testing has to be able to be done in order to make sure you identify patients who are appropriate for gene therapy. In addition, at least in the state of Ohio, our gene therapy teams, as well as payers, have gotten together to determine the most appropriate guidelines for who is eligible for gene therapy.

Then, once you're an authorized gene therapy center, you really have to be able to integrate the transplant team and the hematology teams to make sure that they're integrated in terms of continuous follow up for the patient as they're going through the collection process and as they're going through the transplant process, and then back to the hematologist once they're done with the gene therapy process.

How do you speak to patients/families about whether they might be a good candidate for SCD gene therapy?

Unfortunately, gene therapy is not available for our sickle cell C patients, so that already reduces the number by a third, but I think it's important to present transformative therapy to every patient who would be potentially eligible for it. Having that open, honest conversation with them is important to be able to say, "Hey, we can help you potentially have a significant benefit from doing gene therapy or bone marrow transplant," and sometimes have those hard conversations of having them see the consult service, and having them see the transplant team, but then going back and saying "Okay, what questions do you have that I can help answer in terms of concerns or issues you might have?" Sometimes, as the hematologist, you get a little bit more grace when you have to answer some of those questions about the challenges for gene therapy, about what the outcomes of gene therapy are, and then what the potential benefits are to it.

Sometimes patients are reluctant and decline going through it because of any number of variables, [but also] you get patients who are super excited about it and are ready to jump in today. But the process itself is a long process, too. Sometimes we're looking at 9 months to sometimes a year and a half from first having the conversation with the transplant team to actually getting their gene therapy product, and then another 3 months after that to actually go back to the hematologist. So it's a long process, and sometimes that's the barrier.

Has the integration of gene therapy changed the way that you work with specialists in other fields?

To some extent, yes. At our center, what we've done was integrate the care coordinators from both teams, and obviously the hematologists and the transplant teams work together very well. And so we've integrated both and as patients go through the process, we're able to guide them and help them based on whether something is a transplant question or a hematology question. While they're going through that year to year and a half of collections and monitoring, etc., we have the ability to help comanage in some ways, and then when the other service needs to take over, they can do that, but then they're right back to the other team when they're ready to come back.

This transcript has been edited for clarity.

For more coverage of ASH 2025, click here.