Overcoming Delays in CAR T for Large B-Cell Lymphoma

In part 2 of this interview with Frederick L. Locke, MD, lead investigator on the phase 1 ALPHA (NCT03939026) and ALPHA2 (NCT04416984) trials of allogeneic chimeric antigen receptor T-cell therapy (CAR T) in relapsed/refractory large B-cell lymphoma (LBCL), explains why this hematologic cancer is such an attractive target for CAR T, specifically allogeneic, which uses healthy donor cells.

In part 1, Locke explained how CAR T-cell therapy works and the differences between autologous and allogeneic CAR T-cell therapy.

Locke is chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and Research Institute, in Tampa, Florida.

This transcript was lightly edited for clarity; captions were auto-generated.

Transcript

What specific characteristics of relapsed/refractory LBCL make the blood cancer a promising target for allogeneic CAR T?

We have 3 FDA-approved autologous CAR T-cell therapies for relapsed and refractory large B-cell lymphoma that can be treated. Patients can get those treatments as a third or later line with 3 different FDA-approved treatments, and 2 of those are approved to be given in the second-line setting. They work remarkably well for large B-cell lymphoma.

Large B-cell lymphoma is a cancer of the B cells, the B cells in the body, and it generally grows pretty quickly, and we can actually cure some patients with frontline chemotherapy. That's great, but we're only curing 60% to 70% of patients, and that means many are going to progress and need additional therapy, and oftentimes that's CAR T-cell therapy.

When we use autologous CAR T cells, we have to collect the cells from the patient's blood and turn them into CAR T cells, and that's a process that takes time. It could take 4 weeks or longer to wait for those cells to be manufactured. When we use healthy donor cells, we can give them almost right away because we've already have them premade. There's a huge advantage to using allogeneic CAR T cells vs autologous CAR T cells. And large B-cell lymphoma has proven to be sensitive to autologous CAR T cells, so we want to extend that into the allogeneic space.