Exploring The Donor-Derived CAR T-Cell Therapy, ALLO-501A

Michael T. Tees, MD, an associate member physician at the Colorado Blood Cancer Institute and part of the Lymphoid and Autoimmune Disease Groups, discusses chimeric antigen receptor (CAR) T-cell therapies, including ALLO-501A, and its use for patients with relapsed or refractory large B-cell lymphoma (LBCL).

ALLO-501A is an anti-CD19 allogeneic CAR T-cell product with a disrupted TCRα gene and an edited CD52 gene. Based on early research, the agent may reduce the risk of graft-versus-host disease, and allow the use of the humanized anti-CD52 mAb, ALLO-647 to decrease the number of host T cells for patients.

The agent was first evaluated in the ALPHA1 study (NCT03939026) where no dose modifications or dose-limiting toxicities were observed, and the most common adverse events (AEs) reported consisted of anemia, leukopenia, neutropenia, and thrombocytopenia (73%), and lymphopenia (64%). Then, the ALPHA2, (NCT04416984) study continued to explore the safety and efficacy of ALLO-501A in patients with relapsed/refractory LBCL.

TRANSCRIPTION:

0:08 | CAR T-cell therapy has been around for quite some time. It's been about 5 years since the first CAR T product was approved by the FDA, which was an autologous product. It's the patient's own cells that are genetically re-engineered to recognize that the cancer is foreign. Typically, it's CD19.

0:37 | ALLO-501A is a clinical trial evaluating not autologous CAR T cells, but allogeneic CAR T cells using cells from a donor population to achieve the same effect as using your own cells. [There are multiple reasons] why this is important to investigators. Primarily, there is a lag time between when we need to collect those donor cells and send them away for re-engineering until we can do the treatment for the patient. That lag time can be dangerous and potentially deadly for those patients who have refractory diseases. Having an off-the-shelf product ready to go, if it's safe, is key. We would not have the potential 3-to-4-week lag time of the processing and collection, which is extremely important.

1:54 | What we're also seeing now is a backlog for the products that are commercially available because they can't keep up with that demand. With this agent, the product is ready to go from a different donor with comparable benefit and efficacy, and ideally, an even better safety profile would make this the ideal situation.