Graphic: How do I pick the right therapy option?
Dr. Palmer:
It's really a good question to have. It used to be that we didn't have anything, and then it was that we had one option. But now, we are getting multiple options that are FDA-approved, as well as multiple options that are in the pipeline that hopefully will be approved within the next few years.
So I think when we first think about how we approach the treatment for myelofibrosis, we think, well, what are the problems that we are having? Such as bone pain, fevers, night sweats, weight loss. As well as potentially, spleen symptoms, such as feeling like you get fuller earlier, abdominal discomfort. In that setting, JAK inhibitors are a really good option.
It used to be that we only had ruxolitinib or Jakafi, and in that case, that was the one option we had. And we were really limited by people who were anemic who had low platelets. Then fedratinib (Inrebic) became available in the last couple of years, and that has really been a very good option for patients once they progress through Jakafi.
However, one of the newer things that's coming through is a drug that was just approved earlier this year, called pacritinib or Vonjo. And that has expanded our ability to use JAK inhibitors to include people who have low platelets. This has historically been a group that's really difficult to treat because they can't use fedratinib. They can't use Inrebic or Jakafi in somebody who has low platelets, specifically, below 50. But Vonjo is a very nice option there that has been shown to reduce spleen size, improve symptom burden in patients who have myelofibrosis and low platelets.
A drug that should hopefully be approved within the next six months to a year is a drug called momelotinib. And what momelotinib is, it's another JAK inhibitor, but it's very good for patients with anemia.
As I think of, how do I approach with the current drugs available and I think of different JAK inhibitors, I really base it on what the blood counts look like. So in somebody who has good adequate platelets, good red blood cells, Jakafi or Inrebic are the first two drugs that can be considered. I generally start with Jakafi because Inrebic has been shown to be beneficial to patients who progress through Jakafi, but either one of them can be used in the frontline setting.
In terms of patients with low platelets, then that patient, I would choose Vonjo. I think it's a great option for patients who are in that situation. And then hopefully at some point, we will see patients who have anemia, we can use momelotinib, once that gets FDA-approved, and that has really been beneficial in that patient. So I think, as we look at the role of JAK inhibitors and how we choose a lot of it's really going to be based on blood counts. And the choice to use JAK inhibitors is largely based on the symptom burden as well as spleen enlargement.
Now, one of the coolest things coming out is, now we are having agents we can add to JAK inhibitors. And by adding these agents to JAK inhibitors, we are able to potentially get a response to come back, or potentially, even change some of the biology of the disease. That we don't know yet. That's a little bit hypothetical, but it is something that we've been thinking of.
And there are three drugs that are being tested in phase III studies, which hopefully means, in the next two to three years, we should see approvals. The three drugs are pelabresib (CPI-0610), parsaclisib (Incyte), and navitoclax (ABT-263). And these three drugs are very exciting, and I'm looking really forward to seeing what the phase III studies show. And I think, as we see more data coming out from the phase III studies, number one, we'll understand how to use them best. And number two, we'll understand which patients they're best suited for.
Graphic: When should I consider changing therapy?
Dr. Palmer:
So when do you need to change therapy? That's a big question that comes up. Many people have been on Jakafi for a number of years. They are doing extremely well on it. But now, there are all of these new agents. So when do we change? When should we consider new therapeutic options? And that's something that is very dependent on what's available. Right now, with the fact that we have different JAK inhibitors, I think one of the hardest transitions is when to go from something like Jakafi to something like fedratinib or Inrebic, which is a very good second-line option. And what defines progression is not as well-clarified. I mean in clinical trials, we have criteria such as a certain degree of spleen involvement, a certain degree of worsening of symptoms.
However, I think, when it comes down to clinical practice, it's very challenging to say, "Well, when do I make this decision?" So, one of the typical things we'll see, especially in somebody who's on Jakafi, who's starting to show signs of progression is that all of a sudden, their blood counts drop while they're on Jakafi. So then we say, "Well, we need to lower your dose of Jakafi," because your platelets dropped, or your red blood cells dropped, or something like that. And then we start to drop the dose of the Jakafi, we have less JAK inhibition, and peoples' symptoms come back, and their spleen starts to get more enlarged.
And then at that point, we know, okay, you know what? This is probably not working as well. And especially, as we get to lower and lower doses of Jakafi, we know that the drug is less effective at doing what it's supposed to do. And because of these limitations imposed by blood counts dropping, we have to lower the dose. So that is one situation where we would consider switching to another drug.
Now, generally speaking, if the problem is low blood count limiting our use of Jakafi, that is when we want to be thinking of things like Vonjo or momelotinib, which hopefully will be approved shortly. Because both of these drugs have their own separate way of dealing with patients with low blood counts. For example, if somebody's platelets drop below 50. Even while on treatment with something like Jakafi, we may stop the Jakafi or lower it. The platelets will go up, and they need JAK inhibition. We can go to Vonjo at that time.
And with regards to anemia, that's a little less concrete in terms of what degree of anemia you should really use for momelotinib. Some of that will be dependent on what the FDA says, and some of that will be dependent on provider preference and patient preference. Sometimes people are like, "You know what? This is working. I'd rather stick with what I know than deal with something that I'm not sure how I'm going to react to." Other times you say, "This isn't working great for me. I really want to try something different." And so that's one setting.
Now, the other setting is somebody who's on standard doses of Jakafi and doing fine on standard doses of Jakafi. And all of a sudden, despite that, the spleen starts to get more large, the symptoms start to come back, even without changes in the dose of Jakafi. And that's a setting where you would consider switching to a drug like Inrebic. Because we know that in about 30% of patients who have progressed through the Jakafi, that Inrebic can really help improve their symptom burden and shrink their spleen.
And so these are things that, again, become a discussion between patient and provider to say, "When are we really going to try to pull this trigger? What are your feelings about it?" Because there's really not a concrete right answer of, "Oh, this means you've progressed. This means you changed therapy." It is an ongoing discussion. And it's a great time that we actually are able to have that discussion because it was something we previously couldn't have.
I think it's going to get even more challenging when we have some of these newer therapies approved. Some of the drugs that we can add on to JAK inhibitors and try to say, "When is the right setting for those to be added on? Should we be trying those frontline?" And I think a lot of those questions are being studied right now in clinical trials, and hopefully, we'll have the answer in the next couple of years.
