Dr Houston Holmes Discusses CAR T Therapy Adoption and Education

With chimeric antigen receptor (CAR) T-cell therapy being so new, there is going to be a learning curve as providers become more educated about the treatments, the manufacturing process, and the toxicities, Houston Holmes, MD, MBA, FACP, a medical oncologist with Texas Oncology, explained at the Community Oncology Alliance’s (COA) 2018 Community Oncology Conference.

The American Journal of Managed Care^® (AJMC^®): How familiar do you think community oncologists are with the efficacy and toxicity data on CAR T therapy?

Houston Holmes, MD (HH): So, I think there is definitely a learning curve. Some people are way more familiar with it and others are still learning about it. You know [CAR T therapies were] recently, just last year, approved. And it’s a pretty small number of patients in the country that actually will be eligible. Maybe, ballpark, 5000 people a year. So, it’s not something that everybody is going to be seeing necessarily. So, there is a learning curve and people are becoming more aware of it, but there is still more to learn.

AJMC^®: What is the best way to disseminate information about CAR T therapies?

HH: Meetings like this [COA’s Community Oncology Conference], and I think as it becomes more relevant and more and more patients are candidates, more people will learn more about it. Right now, for people who take care of these patients, the important thing to know is that there is an option. It really is an option for people who don’t have other good treatment options at this point. So, it is important for people to know about it. We’ve tried to educate our partners and people referred to our center, but it just takes the effort to let people know what’s out there. And let people know the toxicities are manageable. I mean they’re serious, but manageable, and, in most patients, they go away, and they don’t have any long-term sequelaes.

AJMC^®: How are community oncologists discussing CAR T treatments with patients and educating them on what they are, how they are manufactured, and what the adverse effects of these treatments might be?

HH: There is a pretty thorough education process that we go through with our patients, both for clinical trials and for commercial therapy, and it includes all those things. First, patients need to be aware of the potential benefits. This could potentially cure diseases in certain settings and that’s the whole goal. But there are substantial toxicities, mainly the cytokine release syndrome [and] neurologic side effects that can be seen. There’s a period of several weeks, of up to 4, sometimes even up to 8 weeks, you can see ongoing toxicities from some of these treatments. Usually the toxicities resolve within the first few weeks. So, patients need to stay near the treatment center for ready access and be evaluated frequently in that time. So, if they don’t live near a treatment center, that means living far away from home for a while. And the potential for delayed neurotoxicity is something that people need to be aware of. Because even 8 weeks out, patients shouldn’t drive a car or do anything that could be compromised by confusion or any other neurologic side effects.

An understanding of the manufacturing process is important too, because even if the patient is a great candidate, and ends up going through this treatment, once we collect the cells it takes a few weeks to get those cells back, it takes a few weeks to transduce and send the cells back to us. In the meantime, some of these diseases are aggressive and there may be treatment in the interval before they get their cells. And, then, at least with the products we’re using now, the CD19 CAR T cells, everybody requires this lymphodepleting therapy just before they receive the cells. And then once they receive the cells, that’s very simple, it’s just a small volume bag of cells that’s infused over a brief period of time. And, at this point, a lot of patients receive that in the hospital just because of the early toxicities, but at some institutions it’s done outpatient with close follow up. But there is a pretty substantial risk of some side effects. But mostly they’re manageable. That’s one thing to be aware of. Even though they can be serious and sometimes dramatic, for the most part they’re manageable and patients get better.

AJMC^®: Since CAR T-cell treatments are so new, how are potential long-term side effects and adverse events discussed?

HH: We have mostly short-term follow-up, but at least so far, there haven’t been any serious long-term toxicities. Depending on the specific CAR T construct, sometimes the therapeutic T cells can be detected in the patient’s blood even years later. For other constructs they don’t persist that long. But sometimes you see that. I’d say for intermediate-term side effects, you can see cytopenias—low white blood cell counts—low platelet count. That can be prolonged sometimes. And since patients have, at least with the CD19 product, B-cell aplasia—they don’t have any functioning B cells, so they get hypogammaglobulinemia and sometimes need IVIG [immunoglobulin administered intravenously] replacement to prevent infections. So that can be an ongoing concern. So far, we haven’t really seen any issues with the viral transduction vector—the virus that is used to introduce the CAR T-cell construct into the T cell. There has been no issues with that virus, so far. And no increased risk of second malignancies, so far. So, most of the toxicities, so far, have been really short term.

AJMC^®: Recently, 2 former executives from Kite Pharma formed a new company to create “off-the-shelf” CAR T therapies. What would it mean to have something like that available to shorten up the manufacturing waiting period?

HH: I think it’s not so much the waiting period as theoretically there would be less toxicity and you could generate those for almost any tumor type. Theoretically. I think we’re just scratching the surface with this technology, truly, and that’s one approach that looks really promising. But we’ll see.