Barriers to Accessibility for CAR-T

This is the third part of an interview with Renier Brentjens, MD, PhD. For the first part, click here. For the second part, click here.

Renier Brentjens, MD, PhD
Credit: Roswell Park

Between high costs and potential toxicities, the accessibility of chimeric antigen receptor T-cell (CAR-T) therapy continues to have barriers. CGTLive® recently discussed this topic in an interview with Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center.

With regard to toxicity, Brentjens discussed the context of treatment-related toxicity in oncology in general and the ways in which the field has become more adept at managing it. With regard to cost, he gave his view that costs will likely come down over time and that the main concern of academics engaged in research and development should be improving the efficacy of the products.

CGTLive: What are your thoughts on barriers to accessibility for CAR-T products?

Renier Brentjens, MD, PhD: I think that there's 2 things that we often face when we present this data. One is toxicities and cytokine release. I mean, we were one of the first to actually even describe that and I still remember well the first patient that had to go to the ICU, and we didn't know, because it was a patient with leukemia so it could have been infection. Then at the time the algorithm said to give high dose steroids and we were very reticent to do that because what we were witnessing was a fever-like response against cancer. So we didn't want to abrogate that too soon.

So there are issues of toxicity, which often is brought up when we present clinical data. And look, I'm a leukemia doc. I spent years giving high dose chemotherapy to our leukemia patients who would wind up having massive toxicities for anywhere from 4 to 6 weeks. But we get patients through that. I would say that for many of the toxicities, for the most part (and there'll be exceptions to this) we can get patients through that reasonably well. So it's not that I'm not empathetic to the toxicities that these cells can cause—I certainly am, and we certainly have developed algorithms to minimize those toxicities—but I think most of what we do as medical oncologists with any chemotherapy is fraught with tons of toxicities, and so we have to accept that, and we have to deal with it. For now, I don't think it's a reason to stop developing this technology. That's the first point.

The second point that always comes up is the cost. Of course, right now, the cost is quite high. Often what I talk about is flat screen TVs. When they first came out, they were extremely expensive and clearly cost-prohibitive. Nowadays I can go to Costco and pick up a flat screen TV and still spend more money in the meat section (although Costco has very good meats). But my point is that as an academic, that my job is to develop the new technologies, and the hope is as the field spreads, as the the number of commercially available products increases, industry will find ways to decrease the production costs. It may ultimately be that it's off-the-shelf products which conceivably would be cheaper, but I think that the incentive will be at some point for pharmaceutical companies, especially when there's more companies making cells targeted to the same target antigen, to then decrease the cost, to find more efficient ways of making the cells, or to find cells that are potent enough that you don't need as many cells to get the same clinical benefit. So I think that these are certainly really important issues that the field needs to address, but again, much like looking at off-the-shelf therapies and looking at natural killer cell therapies, there's the risk that you get too far over your skis. From our perspective, at least, let's not worry too much now about the costs and the toxicities, which we, again, can manage much better—let's focus on creating a CAR T-cell based on our understanding of tumor immunology that can reliably and readily eradicate metastatic disease. When we get to that point, then absolutely all efforts should be made to focus on more rapid production, more cost-effective production, and better algorithms with regard to the toxicities that these cell therapies cause.

This transcript has been edited for clarity.