Studies of CAR T Cells for B-Cell Malignancies

Lori Leslie, MD, assistant professor, Hackensack Meridian School of Medicine, director, Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs, John Theurer Cancer Center, discusses ongoing clinical trials that are exploring chimeric antigen receptor (CAR) T-cell therapy for the treatment of B-cell malignancies.

TRANSCRIPT:

0:08 | There are a lot of other studies looking at CD19 CAR T cells across different B-cell malignancies. We've got ZUMA-2 which looked at indolent lymphomas and led to an approval in follicular lymphoma based on overall response rate of 94% and a complete response rate close to 80% in patients with relapsed/refractory disease. I think further follow up from ZUMA-5 [NCT03105336] will let us know if this is a potentially curative option for our patients with the more indolent lymphomas, they can have relapses 10, 20, even 30 years down the line.

0:40 | We have CD19 CAR T approved in DLBCL and that is being investigated in earlier lines of therapy. Recently published in a New England Journal of Medicine is the ZUMA-7 [NCT03391466] study that looked at CD19 CAR T-cell therapy axicabtagene ciloleucel [axi-cel; Yescarta] as second line therapy compared to standard of care, high dose therapy and autologous stem cell transplantation. This was the first initiated and first to meet its primary efficacy analysis among many different studies in this space trying to transform second line DLBCL therapy, away from high dose chemo and consideration of autologous stem cell transplant, particularly for patients with chemo-sensitive disease and instead sparing patients the toxicity of high dose chemo and transplant and allowing them to go straight to CD19 CAR T-cell therapy in the second line setting.

1:31 | We are taking the CD19 CAR T cells and adjusting the types of lymphoma where we can use them and the lines of therapy where we can use them. Moving forward, what's probably transforming this space the most are potentially CAR T-cell products that target different antigens on the tumor cell, but also dual targeting CAR T, so these targets CD19 and there are other CAR T products that target more than 1 tumor antigen. Instead of autologous products, there are allogeneic off the shelf or their cell therapy products that may be T cells, they may be NK cells. There are some other ways of conjugating an antibody to an effector T-cell to have a CAR T-like effect with a more simple and potentially less expensive manufacturing process. There are a lot of ways that this space is moving forward quite rapidly in a way that's incredibly hopeful and promising for our patients.