Allogeneic CAR T-Cell Therapy Potentially Reduces GVHD Risk

Michael Tees, MD, a hematologist-oncologist at Colorado Blood Cancer Institute, discusses the preliminary safety outcomes observed for an allogeneic chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma.

CAR T-cell therapies made with donor cells can potentially be given more quickly and affordably than autologous therapies that are currently available, but allogeneic CAR T-cell therapies, like allogeneic hematopoietic stem cell transplants, can cause graft-vs-host disease (GVHD).

ALLO-501A, which was studied in this trial, has a disrupted TCRα gene meant to reduce the likelihood of transplanted immune cells harming the host. Tees says that in early trials of this product, there was only 1 documented case of GVHD, which was a patient with possible low-level GVHD of the skin.

Tees notes that this is not the only safety signal to be concerned with, as cytokine release syndrome (CRS) and neurotoxicity can also limit the use of CAR T-cell therapies. As trials of this agent continue, he hopes that a donor-derived CAR T-cell product will also help reduce the incidence of CRS.

TRANSCRIPTION:

0:08 | What ALLO-501A is, is a genetically reengineered product to reduce the likelihood of an argument between the donor and the recipient. One of the initial concerns was using someone else's T cells to fight the malignancy is that potential risk of GVHD, and that's what we see in [patients with] allogeneic stem cell transplant where donor hematopoietic stem cells grow into an immune system that can potentially argue with the recipient. In early ALLO-501 trials, I want to say that there was 1 patient with low-level, cutaneous GVHD, and it’s a question on whether that was a true [adverse event]. That risk has really been demonstrated to not be an issue. We can safely infuse these T-cell products from a different donor into a recipient.

1:09 | The next phase of this is efficacy and safety. There are other safety signals that we need to be looking at for CAR T-cell therapies such as cytokine release syndrome [CRS] and neurotoxicity. The current products that are available for patients commercially do have a high incidence of CRS and neurotoxicity. I am hopeful that perhaps having a donor-derived product can reduce the severity of CRS.