AJMCtv® Interviews, PCOC 2018

Brian Koffman, MDCM, DCFP, DABFM, MS Ed, Medical Director, CLL Society

As someone treated with chimeric antigen receptor (CAR) T cells, what do you do regarding follow-up? What is your physician keeping an eye out for?

Since CAR T is a new therapy, and the first genetic therapy that’s been approved in the United States by the FDA, I’m being followed for 15 years. Which I’m very happy about, because if I’m being followed for 15 years, that will mean I’m 82 years old, so it means I’ve lived 15 years with this.

I’m being followed to see are there any undiscovered adverse events that we don’t know about. It is gene therapy, I have foreign genes in my body, that’s why it’s a chimera—a mix of 2 different creatures in me. So I have foreign protein in me. Is this going to cause a problem? Other gene therapies have been disastrous in the past. So far with CAR T things have gone well. But is there something that’s going to pop up 5 years from now, 10 years from now? We really don’t know the answer to that. So that’s one thing that I’m being looked at for.

The other thing is how persistent are the CAR T cells themselves? There’s not clarity on how important that is in terms of the duration of the response. So, some people lose their CAR Ts and they still have very durable responses and other people have persistent CAR Ts, but the cancer comes back.

And that leads to the other big question: Do I remain in a complete response? Or is the cancer creeping back again? That’s the main thing that they want. So, in CLL [chronic lymphocytic leukemia], the responses have tended to be quite durable for most patients. But in other blood cancers, sometimes people get a deep response—MRD [minimal residual disease] undetectable—but the disease can be back again in 6 months. So I think that those are the things that they’re looking for.

Plus, the usual kind of things. Am I getting more infections? Am I getting anemic? Am I getting problems with my platelets? Things like that. The follow-up isn’t too onerous. I essentially get a physical exam and blood work once a year.

What have been the benefits and the challenges of being treated with CAR T therapy?

CAR T therapy is very early in its development. So, making a decision to jump into CAR T therapy has inherent risks associated with it. But I decided the risks were worth the potential benefits, which would be an extremely durable response. There are a number of concerns about that. The first is that we don’t know yet how to predict who is going to respond well to CAR T. We also don’t know who is going to get quite toxic from CAR T. These things are not yet predictable, although they’re working on it.

The other thing is, except really for a handful—and I’m talking a couple of patients—we don’t have much data beyond 2 years out. The bulk of people have been treated in the last 2 years, so the 2-year data [are] encouraging. And there’s a handful of patients who are 5, 6, 7 years out [who] are doing well, but I wish there were hundreds of patients, and I wish they were 30 years out and I could see that data. That’s another issue.

When you enter CAR T therapy, there’s this ironic twist, and that is you’re hoping that you’re going to get sick, because the sickness means that when these CAR Ts, which have been re-engineered to attack your cancer—they’re serial killers—they’re going in and killing off your cancer cells. And you get pretty darn sick when all this killing is going on in your bone marrow and in your blood and your lymph nodes are shrinking and your spleen. And this is called cytokine release syndrome. Cytokines are these enzymes that are re- leased when there’s an inflammatory process going on, and it’s like the worst flu that you ever had, and most people need to be hospitalized for this. And you’re kind of hoping that you get it, but not get it too bad, because if you don’t get it—that doesn’t mean the CAR Ts aren’t working—but generally, you have to get a little bit of the cytokine release to get the benefit of the CAR Ts.

Beth Wittmer, RN, OCN, Manager of Care Management at Florida Cancer Specialists and Research Institute

It’s very strange to get a therapy that you hope you get sick with, because that means that it’s working. Having said that, and I was extraordinarily sick, I had a really bad time, but I got what I came for. When I was restaged, this cancer, which was 60% of my bone marrow, was gone to the best testing of something called MRD undetectable, or minimal residual disease undetectable, down to 1 in 100,000 or maybe 1 in 1 million cells. They could not find it anywhere in my blood or my bone marrow.How are patients educated on the risk of neutropenia when they’re treated for cancer?

Any patient coming to Florida Cancer Specialists does education prior to starting or on the day of starting their chemotherapy, but there are many that are oral patients that maybe don’t ever go into a treatment room. So, our care management department helps manage all of those patients, and with that, we talk about the side effects of chemotherapy, with neutropenia being one of the most potentially lethal to them. So we talk about those precautions and we sort of have templates built, as well as patients calling in after hours, and we have a neutropenia protocol that we follow as well.

Are there strategies to treat patients quickly in the office before they have to go to the emergency department (ED) if they have neutropenia?

And that’s our goal: to try to keep them out of the ED. So, one, being proactive in calling the patient. If they finish the treatment, so this is from the care management perspective, the nurse is calling the patient to see how they’re doing, what kind of adverse effects they’re having. Fever, of course, is the number 1 sign to watch for with neutropenia.

And as their white cells drop, their neutrophils drop. Neutrophils are your front line of fighting off an infection. So if you don’t have the neutrophils there, the body’s response is different. It doesn’t say, “Hey, guys, we need your help from the macrophages and everybody else to come in and help surround the infection.”

Also, educating on foods that they should avoid: raw foods; raw vegeta- bles, especially salad; berries, because they’re a little harder to wash, they can carry bacteria that normally our gut can handle, but someone who’s neutropenic can’t.

So just making them aware of what to be cautious about. Check your temperature and report any symptoms that you’re having. And then, if we can, we take them in to see the physician, into our own clinics, if we can help that. Either bringing them in for potentially reviewing their [complete blood count] again, putting them prophylactically on antibiotics. Sometimes those are done [intravenously] in the clinic, as well.

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