How Do You Know If Your NHL Treatment Is Working?

Dr. Evans:

Hi. Dr. Andy Evans. I am Associate Director of Clinical Services at the Rutgers Cancer Institute of New Jersey, and also Medical Director of the RWJBarnabas Health Oncology Service line.

What Are the Frontline Treatments for NHL and How Do You Know if They are Working?

Dr. Evans:

Yeah. So frontline treatments, as you could imagine, kind of go back to the original part of the discussion of, what exact subtype do I have? And obviously, there's some – that's the disease. That's the lymphoma subtype. Then obviously, there's some patient-related factors. Is this a 23-year-old young woman with primary mediastinal diffuse large B cell lymphoma? Or is this an 81-year-old man with P53 mutated mantle cell lymphoma?

Well just based on age alone, sometimes, there will be some different treatment recommendations, different treatment intensities. So in terms of a standard of care, it really goes down to those individual factors. In other words, individual – what exact subtype do I have? And usually, within the biologic pathologic subtype, you'll usually have anywhere between one, to three, to four, kind of options. And then you apply the individual patient factors: age, comorbidities, patient wishes, et cetera, to look at the pros and cons. You might have a little more aggressive option, a little more conservative option, where it becomes not a right answer. And again, circling back to the concept of shared decision-making.

And that's where that initial staging comes into play. So it usually ends up being, besides basic blood studies, that PET scanning or CT scanning. One or the other, depending on the situation. And again, our goal, more often than not, we want a complete remission. In other words, wherever it was before, no matter how many places, by the end of treatment – and we usually do a check halfway during treatment. We want it gone from everywhere.

What Are the New and Emerging Therapies for NHL?

Dr. Evans:

The good news is, there are a ton of new and emerging therapies, and we have loads of cancer research laboratories. And I can tell you, I don't think anyone's studying new chemotherapy. Not to say we don't use it. Chemotherapy’s important. It helps us with cure. But where we're either adding on top of chemotherapy platforms, or, in some cases, taking away and substituting chemotherapy drugs, or with so-called targeted agents.

And that's a big-picture term. And we talked about the – going back to the biology, back to the lab, so to speak. That's where we can look in the laboratory, the surface of the cell. What kind of sticks out of the surface? Certain proteins can give us a target, and we are multiple monoclonal antibodies. It's an IV, but very targeted.

So unlike lymphoma, that just kills anything growing fast in the body – that's why sometimes there's hair loss. It's one of our fastest-growing cells. Chemo tends to be a little nonspecific. These are more targeted. It goes right to the lymphoma cell or inside the cell. When we talk about DNA/RNA changes, there are drugs, multiple, that are approved, to literally target what's inside the lymphoma cell and making it grow.

And sometimes there's not – I would say, in most cases, there's not one master process that helps lymphoma cells grow. That you might need to cobble together an antibody with a targeted drug, et cetera. And – oh, by the way, also, with some of these antibodies, you can attach things onto it. And, almost like a smart bomb, deliver the little pieces of chemo or radiation. Deliver it to the lymphoma cell. And it's just remarkable.

And another category, just a huge breakthrough of cancer treatments. You might hear the term immunotherapy. And that could have a few different meanings. Some people say, "Well, you're targeting the immune system. That's immunotherapy."

I think, in the purest sense, what immunotherapy is, literally stimulating and using the patient's own immune system to treat the lymphoma. One class of drugs, to that point, are called “checkpoint inhibitors,” which is just a remarkable class of drugs. Why? Because what they basically do, at the real high level, is they stimulate the patient's own immune system to go after the cancer. And what's remarkable about that class of drugs is, it's not just approved in lymphoma, in multiple solid-tumor cancers as well. You might have one checkpoint immunotherapy inhibitor that, again, stimulates the patient's own T cells’ immune system to fight the cancer.

And literally every year, we have a multitude of new targeted drugs being approved. And that goes back to clinical trials and the importance of clinical trials. Because the only way to get these new, exciting, breakthrough, targeted drugs approved are through clinical trials. It's how we make progress. It's how we push the envelope. Not only increase cure but actually, at the same time, maybe improve quality of life, relatively speaking, especially if we're replacing a chemotherapy drug. So it's just an incredibly exciting time in the field of lymphoma, in terms of new, targeted lymphoma treatments.

And there are a host of other therapies. There's even another breakthrough category. I'll use that term of something called CAR T-cells, chimeric antigen receptor T-cell. So it's a little bit of a different but similar concept. You're basically taking out part of the immune system, T cells in this case. Sending it to a company, or, in our case, we have a GMP (Good Manufacturing Practice) laboratory. We can make our own cells. But somebody – basically, you take the cells, the T cells, that we know aren't working because there's cancer in the body, these T cells. And you basically make them stronger, in a way, these T cells, and you could even – what's called “transfect” an antibody onto it. So when you reinject it a few weeks later, it not only expands in a strong manner to treat the – in this case, lymphoma. It goes to the lymphoma in a targeted fashion. And we're just scratching the surface on these CAR T-cells. There's other constructs, immune constructs I should say, that we're exploring for the benefit of lymphoma patients.

What Is the Life Expectancy for NHL?

Dr. Evans:

Yeah, it's tricky. Is it newly diagnosed? Is it relapsed? Hopefully, we're in the relapsed context. As you could imagine, it goes all the way back to, what exact subtype is it? Patient age? Do they have other comorbidities? The stage enters a little bit into that. But generally speaking, I would say many of the lymphomas, especially, as you can imagine, if they are curable; well that would be a normal life expectancy out of the gates. Now, are there some, where it's not a normal life expectancy, but we've improved survival? Where we're getting close to normal life expectancy? Yes, there is.

But, at the end of the day, especially for those aggressive lymphomas, our goal is cure. In other words, go away. Never come back. Have a normal life expectancy. But, by the way, that's not to minimize, even in the curable lymphomas, non-Hodgkin’s, or Hodgkin's, great. You've cured the lymphoma. There are some things that – I'll use the term “late effects.” And that comes to where survivorship is so important. Why, you really can, even after treatment and cured, you always want to stay in contact with your oncologist, or, at least, someone who understands the concept of survivorship. Because sometimes, five years later, 10 years later, there might not be a risk, or really inconsequential risk of lymphoma coming back. But there can be some late effects due to the treatment: sometimes cardiac, pulmonary, immune compromise, et cetera. So, always good to keep in context. Okay, great. Might be in the normal survivorship or normal life expectancy, but I want to make sure nothing else picks up later down the road.