Challenges Surrounding CAR T-Cell Therapy in Follicular Lymphoma

Sattva S. Neelapu, MD, a professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, discusses the challenges surrounding chimeric antigen receptor (CAR) T-cell therapy for the treatment of follicular lymphoma and other lymphomas.

According to Neelapu, while the response rate stands at around 80%, only about 35% to 40% of patients will have a long-term remission. This may be for multiple reasons, including the dysfunctionality of the CAR T cells or due to previous chemotherapies received by the patient.

However, CAR T cells from a healthy donor could help overcome some of these concerns as the fitness of the cells will be much higher than those from the patient. According to Neelapu, an over-the-counter product offers other benefits. For example, a product would not need to be manufactured, meaning the turnaround time would be quicker. Patients would not need to spend lengthy periods of time at one of the country’s few CAR T-cell centers. In addition to improving efficacy, an over-the-counter product could help expand access. 

0:08 | Autologous CAR T-cell therapy, so there are at least 2 CAR T autologous CAR T products that are currently FDA approved for relapsed refractory large B-cell lymphoma. This option does not impressive efficacy here with response rates up to 80%, but only about 35% to 40% of his patients have long term remission. So, if we look at why the 60% of patients relapse or progress after autologous CAR T-cell therapy, there appears to be multiple reasons. So, one of the reasons obviously, is because the CAR T cells are dysfunctional because the T cells in the patient could be affected either because of the disease, the lymphoma itself, or because of the chemotherapies that these patients receive. So, if we were to take CAR T cells from a healthy donor that could potentially be overcome, because the fitness of the T cells would be much better compared to autologous CAR T.

1:11 | But besides that, there are other challenges with autologous CAR T-cell therapy because the logistics of manufacturing come. It is a patient specific CAR T product. So, it takes on an average of at least 3 to 4 weeks turnaround time from the time we collect the pieces from the patient to when we can actually administer the CAR T cells to the patient. This could potentially be overcome by off-the- shelf CAR T-cell therapy approach from a healthy donor.

1:47 | In addition, when we look at what percentage of the patients we actually get referred to autologous CAR T therapy, who actually received the product, we see that at least at our center, somewhere in the range of 10% to 15% of those patients who get referred to our center for commercial CAR T don't end up getting that CAR T product. The main reason for that is because of the delays in the manufacturing, the 3 to 4-week turnaround time. Besides that, if we look at the numbers of patients who are treated with autologous CAR T in 2019 across the US, for example, the estimates are that only 20% of lymphoma patients who actually need autologous CAR-T cell therapy are actually receiving it. So, 80% of the patients are not receiving it. And that I think it's partly because of the accessibility.

2:46 | So currently, autologous CAR T is being administered at approximately 80 centers across the US, which averages out to only one or two centers per state, which is clearly not enough. And to receive autologous CAR T-cell therapy, the patient and the caregiver, need to travel to a CAR T center, need to stay locally for at least a 5 to 6-week period, which is not practical for most patients. On the other hand, if you were to have an off-the-shelf CAR T approach, it could potentially improve the accessibility because it simplifies the logistics and infrastructure that is required to administer CAR T-cell therapy. For example, a center is not required for allogenic CAR T-cell administration only. All the centers would need is a liquid nitrogen freezer to be able to freeze the product and keep it in storage until administration to the patient besides the standard infrastructure required for patient monitoring and management of any adverse events.