Future Directions for CAR-T Therapy



Leo Gordon, MD: People have wondered about the cost, expense, and design of CAR T-cell treatments. The cells have to be made for each individual patient. Is there a possibility of off-the-shelf treatments? People have done that with natural killer cells. It’s quite possible it’s going to happen. We’re going to have to get around human leukocyte antigen [HLA] barriers and a variety of other obstacles to do this. Down the road, as people start developing their own CARs, the treatment will certainly become cheaper.

Making CAR T cells is not that difficult to do now. There are instruments that help you do it in just an hour—maybe even minutes. The scale-up that you need can be very expensive for single institutions. Pharma has 3 fairly large, reasonably sized companies like Kite Pharma and Juno Therapeutics that were eventually bought by bigger companies because the cost of producing these treatments and conducting the clinical trials was immense, with the scaling-up required for building and manufacturing plants.

Matthew Lunning, DO: We have to first traverse the inpatient/outpatient ability to administer CAR T cells. If, in the future, there’s a construct that has equal efficacy and toxicity profile, which is reminiscent of outpatient chemotherapy regimens that we administer, we can get a cytokine release syndrome [CRS] and neurotoxicity management plan in place. We still have to tackle being able to give lymphodepletion and CAR-T cells to outpatients close to the center.

I’m all in this for patient access. If there are patients that cannot get CAR T cells because they cannot travel 400 miles to the nearest CAR T-cell location, we have to give those patients the ability to get to a center that has the ability to give CAR T cells. We’ll continue to expand the radius of people that we can treat. We also need to educate the people in the community about CAR T cells because it is a multidisciplinary effort.

I take the patient through their CAR T-cell therapy, and they stay for a certain period of time thereafter before they return home. Now they’re returning home into the hands of their community oncologist. You can be certain that I’m talking to the community oncologist about whether they checked for cytokine release syndrome. Did they have neurotoxicity? And then I would show them how we managed it. We’re educating them on what CRS and neurotoxicity look like, and which strategies we use that are widely accessible. I want to be reached out to if one of my patients is experiencing neurotoxicity or CRS after they return to their community. If they receive that level of education, then there’s a construct out that could provide the efficacy and safety admitted for treatment.

If you look at the curves, a population of patients who otherwise were likely to be next in line for therapy would, in effect, not benefit. But it doesn’t mean that we’re done; we still have a lot of work to do to improve upon CAR T cells by adding additional therapies, to make the CAR T cells more effective, or try to manipulate the construct itself to increase efficacy and decrease the toxicity profile.

We have to think about the patients out there; I always come back to patient access. We need to find a way to increase the exposure that there are options for high-risk lymphomas for patients and providers, so that they can realize that relapsed/refractory diffused large B-cell lymphoma has 2 approved constructs, and that there are clinical trials using CAR T cells and making advances.

They may be eligible for a different clinical trial if CAR T cells are not beneficial for their disease. I implore trying to find new ways to reach out to patients and providers at non—CAR T-cell centers. I may be able to say, “I have a friend and a colleague here who’s 300 miles closer to you—here’s their number.” I have no ego in this; I’m trying to help them; I want to do what’s best for the patient. We can continue to receive better CAR T-cell spaces, but I need to acknowledge that relapsed/refractory diffused large B-cell lymphoma remains an unmet medical need.

Transcript Edited for Clarity

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