EBMT 2025 | Is there a risk of infection and a need for re-vaccination after gene therapy?

As we have started treating more and more patients with gene therapy, a number of things are becoming apparent to us. There are certain similarities in gene therapy to allogeneic transplantation, for example, the use of chemotherapy prior to infusion of the genetically modified cells. But then at the same time, there are a number of differences. And one such difference is that these patients who have received gene therapy, their immune system remains relatively intact after undergoing gene therapy. 

So after allogeneic transplant, we are used to seeing a prolonged period of immune deficiency. Patients are receiving graft-versus-host disease prophylaxis, which further suppresses their immune system. And then it takes several weeks to months for their immune cells to recover completely, for them to have a complete immune reconstitution. We often vaccinate or re-vaccinate individuals after allogeneic transplantation to prevent vaccine-preventable diseases for which they might have received vaccinations previously. 

Now in contrast to this, what we’ve seen is, because we only use single-agent busulfan for most of the patients with gene therapy right now, and there is no lymphoablation or no immuneablation involved in this process, many of these patients actually retain their immune system immediately after they have undergone gene therapy. So they have normal lymphocyte counts or near-normal lymphocyte counts. They also have retained immunity to many of the vaccine-preventable diseases that they have been vaccinated against. And so these patients have a very different immune reconstitution, and they may not need the same level of immune surveillance or immunoprophylaxis. 

For example, in allogeneic transplant patients, we are very used to following viral serologies, looking for EBV, CMV, adenovirus quite frequently after transplantation, and allogeneic transplant recipients are also at a very high risk of developing these infections. That has almost not happened in any patients who have undergone gene therapy. We don’t see widespread CMV, adenovirus, or EBV disease in gene therapy recipients. Likewise, the period of neutropenia is very short in these patients, so the risk of bacterial infections is also low. 

Having said that, though, mucositis is a real problem in patients with gene therapy because of the use of myeloablative busulfan. So I believe that the immune surveillance and immune monitoring practices are a little bit different, and we have outlined them in our manuscript that was recently published in Cytotherapy, talking about what are the different considerations for patients who are undergoing gene therapy. And once again, I believe that many of these patients will retain their immune memory against vaccine-preventable diseases. So it’s advisable to check for those titers against the vaccine-preventable diseases before revaccinating everybody empirically after gene therapy.

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