What are the NCCN Treatment Guidelines? What strategy should be used in selecting a therapy?

What are the NCCN treatment guidelines?

What strategies should be used in selecting a therapy at relapse?

So NCCN is the National Cancer Consortium guidelines, and it's basically a treatment and diagnosis guideline that's made by expert oncologists throughout the United States in all the different cancers. It really has two purposes. One is to help doctors because most physicians out there don’t see just one cancer. They see prostate cancer, breast cancer, colon cancer, leukemia.

And they may have one or two myeloma cases per year, so the standard of care treatment, which changes so, so quickly, they’re not aware of. They don’t know exactly what the most updated treatment is, and the NCCN guidelines are a quick reference, constructed and made by experts in the field, about how to choose the right treatment based on certain tests and certain conditions.

So that's really the main purpose of NCCN guidelines. But with those guidelines, the second purpose of it is the insurances use those guidelines to determine what will and will not be paid for. So it's important really to have as many possible treatment options included in those guidelines as possible so that they are paid for by the insurance companies and so that they're considered standard of care.

Even if there is an accepted treatment regimen, but it’s not put in as, you know, first line where it may be used as first line, the insurance company may not pay for it as a first line therapy. So, you know, we use those guidelines. Now, in myeloma, the NCCN guidelines can be extremely confusing for a physician who isn’t familiar with myeloma because there are so many different treatments.

And for third-line treatment, you might see 15 different possible regimens. So you need to know how to pick which regimen for each patient, and that can be sometimes difficult. And as a person who does this only in multiple myeloma, you really have to use the patient who's sitting in front of you as the guide for which treatment is best out of those 15 or even 20 recommended regimens.

You have to understand what side effects those treatments are going to produce, how they're administered.

Sometimes a patient may live very, very far from the cancer center and doesn't have transportation and relies upon other family members to bring them to and from the cancer center, and they cannot take an infusion every single week. It just might not be possible. So you have to look at quality of life factors, financial factors.

And also, you have to look at the speed of the myeloma. How quickly is it coming back? Do you need something that's going to bring it down quickly, or can you do a regimen that might work a little bit more slowly?

So these specifics of every single treatment are really the art of how to pick a treatment for relapse.

They're updated several times a year, and if there's a new article that comes out in a very well-reputed journal, or if there's a new meeting that comes out that talks about a very good treatment, then the updates occur. They occur fairly rapidly.

It’s a very live document.

So if you look at the NCCN guidelines, it's like you're going to the Cheesecake Factory. You know, it’s an amazing menu. There’s tons of stuff. And I think the NCCN guidelines allow the treating physician the opportunity to really find a treatment that is suitable for the patients.

And so that's great that we have options for the patients.

We know that you have to get it right at the time of relapse.

I think we're very mindful of what we’re trying to do and basically to give a guideline for oncologists in the community who may not be in the position of seeing lots and lots of myeloma patients.

The guidelines are meant to do several things. One is, if a person walks in the door with myeloma and they don’t really know what the appropriate evaluation should be, we're very specific about what is considered standard of care.

We also try to sort of outline this would be the first treatment, but then subsequently what you might do at relapse. But the reason the lists are long is that it turns out that there are a lot of different drugs that people with myeloma can respond to, more and more all the time, in more and more combinations.

What we try to do is give a lot of choices. Obviously, what we would love is for people to always go on a clinical trial if that’s an option. But if it’s not, then what we’re trying to do is give people options. Let’s say your patient is potentially a transplant candidate. Okay, here are some things that it would be okay if you're going to get a transplant.

What we do know, and I'm sure your audience is very aware, particularly for people who are of Medicare age, there are some drugs that may not be covered. So, for example, some of the IMiD drugs like lenalidomide or pomalidomide may have no access to those at all because of cost, so you want to have choices in that list.

That includes drugs that would only be given in the clinic covered by Medicare B.

We also want to have choices for people who are not going to transplant, who may not be medically as fit. So the number of choices is not meant to be bewildering. It's more meant to be accommodating for what the realities are in a clinic and what they have to deal with.

What strategies should be used in selecting a therapy at relapse?

So, we're going to start by finding the best combination, because one drug is not going to be enough.

With each relapse, if you don’t get it right, the duration of response and the depth of response is reduced. So if you wait until the third relapse to use your best regimen, or fourth relapse, you're giving the patients less chance of living the longest and surviving myeloma.

So you really need to get it right at the first relapse and use the best combination you can at that point. Nowadays, what's approved is a monoclonal antibody with a proteasome inhibitor, with or without the immunomodulatory drugs like pomalidomide, for example, with daratumumab or isatuximab. So there are a lot of options, but you really need to use combination therapy to provide your patient the deepest level of response.

Getting complete remission is a good thing. Getting complete remission that is MRD-negative, minimal residual disease undetectable, is a good thing. That translates to staying without relapse for the longest period of time and also living the longest. So that should be our goal.

NCCN is to have what we call preferred regimens, the ones that we would ideally offer people, and then other regimens depending on the availability of drugs and coverage. So I think we also try to have people, particularly once we’re looking beyond initial treatment, to say, what if that individual developed really bad neuropathy related to their previous treatment?

Well, you may not want to pick bortezomib. That might be something that you don’t want to do. Or let’s say a person is going toward CAR-T therapy. There’s a drug we sometimes use at relapse called bendamustine. You might not want to get that drug as part of your relapse myeloma treatment, particularly if you think you're going to get CAR-T.

We do try to give those tips as we're going through it. But again, the purpose is to expand the options for patients and their caregivers rather than limit them and say, oh, there’s only one or two that are acceptable.

How can patients participate in the shared decision-making process?

A question to ask if your provider says, and you're looking at that list, and it might have ten options for relapsed myeloma: Could you tell me why you picked that particular one for me, and what would make you want to change that?

I think those are two very good questions.

There are different goals sometimes when a person has relapsed. For example, if a person just has blood levels of proteins change and they otherwise feel great, the goals then might be very different, maybe just controlling those levels. Versus if somebody comes in, and they’ve broken a bone, and they are really sick from their myeloma, typically then the choices should be something strong enough to really get that myeloma back under control.

As a patient, you’d want to ask the provider who's seeing you: What are the goals that you're having for me right now? Are we trying to get into remission again, for example, or are you just trying to control things?

The other thing that patients can do that’s very helpful in choosing is—people do this in my state, which is quite rural—they’ll say, I can’t drive 100 miles every week to be in the office.

That’s going to tell you right off the bat that you might want to look at different choices. You were mentioning cellular therapy. We want to be very upfront with patients to say, okay, we’re going to try to help you find accommodations here for the next month while you're here doing this. But that’s another way that, as a patient, you can say, what do I need?

Again, we have people who are working, and we sometimes say, okay, this is something that we actually believe we can get going over a weekend. So you can still be there Monday through Friday doing your job.