What Are the Currently Approved Myelofibrosis Therapies? from Patient Empowerment Network on Vimeo.

Expert Dr. Gabriela Hobbs shares an overview of available therapies and important considerations when choosing a myelofibrosis treatment plan.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Transcript:

Katherine:

Would you provide an overview of the currently approved therapies for myelofibrosis?  

Dr. Hobbs:

Sure, absolutely. So, I’ve alluded to this a little bit. So, in 2011, we had the first JAK inhibitor approved called ruxolitinib, the brand name is Jakafi. After that, we had the approval of Inrebic or fedratinib and then pacritinib or Vonjo, and then most recently momelotinib or Ojjaara. So, we have four different JAK inhibitors that are now approved for myelofibrosis.   

So, who needs to get a JAK inhibitor and how do we choose between the JAK inhibitors? So, the traditional indications for JAK inhibitors are, does a patient have bothersome symptoms from having a big spleen? Does a person have symptoms from their disease? Symptoms can include things like night sweats, itching, unintentional weight loss, brain fog, and fatigue. Fatigue can be challenging because of course many things can cause fatigue. But those are some of the symptoms that can occur with having this disease. So, if a patient has both splenomegaly symptoms or one or the other, they’re eligible for a JAK inhibitor.  

So, just having myelofibrosis doesn’t mean that you need to have a JAK inhibitor right away. Probably the most commonly used JAK inhibitor, and this will be the case probably for a long time, is ruxolitinib.  

The reason for that is that it’s been around for a long time, and it’s a very well-tolerated medication. Patients that have platelets that are very low, meaning platelets that are less than 50, should be considered for pacritinib first, as that’s the indication for that agent. Patients that don’t do that well on ruxolitinib initially, let’s say that the dose gets increased and the spleen and the symptoms are still present, but still have good blood counts, are good candidates for then receiving fedratinib. Fedratinib can also be given upfront. It rarely is given upfront, simply because ruxolitinib has been around for longer and it’s a better-tolerated medication.

So, therefore most providers feel more comfortable giving that upfront. I have had some patients that are concerned about the weight gain that is a side effect of ruxolitinib. For those patients, I’ve occasionally considered giving fedratinib first before ruxolitinib. And then lastly, we have momelotinib. It’s approved primarily for patients with myelofibrosis and anemia.  

Now momelotinib is still a JAK inhibitor, so it can still improve symptoms, and it still improves spleen size. So, I struggle with that recommendation of just using it for anemia in patients that don’t have splenomegaly or symptoms.   

But the FDA label was pretty broad, and it’s important to recognize that. So, how is momelotinib being used? It can be used in the upfront setting for patients that have spleen and symptoms, and also anemia, meaning low red blood cell levels. Or,  it can be used for patients that have been treated with a JAK inhibitor first and then develop anemia. So, momelotinib is given to continue to improve the spleen and symptoms, but also help the anemia.

So, that’s kind of like an overview of the four JAK inhibitors. Now we have a group of patients that maybe doesn’t have a lot of spleen symptoms or symptoms in general but has issues with having low hemoglobin. So, for those patients, we’ve used a variety of different medications, including medications that are called erythropoietin, which is a hormone that helps to boost the red blood cell levels.  

 A medicine that’s similar to testosterone that can also help boost the red blood cell levels called danazol (Danocrine). And then there’s a medication called luspatercept-aamt (Reblozyl) that has been approved for a related condition called myelodysplastic syndrome. And in some clinics, it can be used even though it’s not approved either by itself or in combination with ruxolitinib.

And then lastly, patients that have what is called high-risk myelofibrosis, meaning they have some mutations that may indicate that a patient has a higher risk of having complications of their disease, or they have very low blood counts, are usually considered high-risk. Those patients should be recommended and referred to transplantation as soon as they’re identified as having high-risk disease.  

Katherine:

When you say transplantation, you’re referring to stem cell transplant. 

Dr. Hobbs:

Yes, and I’m glad you said it that way actually. So, stem cell transplantation or bone marrow transplantation, same thing, interchangeable, same procedure. You got it.  

Katherine:

When considering therapy, how do you approach a treatment plan for someone diagnosed with myelofibrosis?  

Dr. Hobbs:

Great question. So, when approaching how I care for a patient with myelofibrosis, I take several things into account. The first thing is, who is this patient? What other medical conditions do they have? How impacted are they by their myelofibrosis? Then what I like to do is to plug in the numbers of the patient, their blood work, their mutations, etcetera, into one of the many risk calculators that we have to determine what the risk of their myelofibrosis is.   

If a patient is considered high-risk, I will generally consider transplantation or discuss a referral to a bone marrow transplantation in one of our first visits, if not the first visit. After that, I need to determine whether or not the patient has symptoms from their disease, and if so, if they should receive a JAK inhibitor. Then I’ll look through their blood work, what their symptoms are to decide which JAK inhibitor to use first.   

If really the spleen and symptoms aren’t the primary issue, if it’s more related to low blood counts, then we can think about treatments directed at improving the hemoglobin, for example. There may be a group of patients that don’t actually require any treatment when I first meet them. So, just providing them with education, what to expect. Then discussing more of the psychological impact of living with a condition and approaches to handle that, maybe more the focus of my care.

And in general, for most of my patients, we also talk about the rest of the care. So, not just what the blood work is and what medicine I’m going to start them on, but also other things that they can do to take care of themselves, including making sure that they are actively monitored by their primary care doctor or by other specialists if that’s still appropriate. You know, one of the things we don’t discuss that frequently in myelofibrosis, we discuss that more often in essential thrombocythemia or polycythemia vera is a risk of blood clots.  

But the truth is that myelofibrosis patients can also have risks of blood clots. So, therefore, making sure that patients with MF that may have issues like hypertension, diabetes, high cholesterol, etc., get those well-managed is also really important to prevent them from having blood clots. So, lifestyle management is also an important part of the care of a patient with myelofibrosis.