What are my options for treating myelofibrosis?

What are my options for treating myelofibrosis?

I tend to think of the treatment options in four different buckets.

First bucket is stem cell transplant. This again is the curative potential therapy option. Again it comes with a higher risk of complications and is not for every patient. And so when I am meeting with patients for the first time, usually the first decision point we come to is whether or not stem cell transplant is something that they would consider as a therapeutic option. Not every patient considers it, and that's okay. And at that point, I usually will get patients over to our transplant team to have that discussion.

The second bucket of treatment options are symptom-based therapies. So therapies that we can use truly just as we think about them to treat patients' symptoms. So management of things like bony pain we can use narcotic pain medications, anti-inflammatories, things that we can do to help with fatigue. I've started to use a lot of low-dose stimulants and other agents to really augment energy for folks to allow them to do what they want to do. We've done things like radiation to the spleen, to help shrink the spleen, and then other adjunctive, such as blood transfusions for blood count abnormalities to help with those particular things.

The next bucket of therapy is the FDA-approved agents that we currently have. And at the moment we have four approved agents for the management of myelofibrosis. They are all within this larger category of JAK inhibitors. And so if you think back to the root of the problem and the cause of this disease, it's oftentimes these driving mutations like JAK mutations. All the mutations create abnormal signaling through the JAK-STAT signaling pathway. And so, multiple individuals have developed drugs called JAK inhibitors, which treat patients and block signaling through that pathway.

So in 2005, the mutation that underlies most myelofibrosis, called JAK2, was discovered. And since then there's been an explosion of research into how do we target JAK2? Is there a way that we can target that and eradicate the mutant stem cells? And so far, we're not there at eradicating the mutant stem cells. But we're very good at treating symptoms with things called JAK2 inhibitors.

JAK2 inhibitors are pills that patients take. They're kind of like a high-power ibuprofen or acetaminophen, where they really help the symptoms of fatigue and sweating, and they can shrink the spleen size, make you feel better. You can eat, you can gain weight again. And those are the backbone of therapy for myelofibrosis these days.

And then the last bucket, which is something that I'm particularly interested in, I think is so important, is the development of novel therapies. And so I think this is an incredibly exciting time for patients with myelofibrosis and really all MPNs because there has been such an interest in developing agents that work in different ways and developing agents that can be used either in addition to current therapies or as new model therapies.

And so when I'm talking to patients, and especially patients who have already tried one of the FDA-approved agents, I always like to think about whether or not a clinical trial may be right for that patient, because it gives folks the opportunity to try a therapy that works in a different way via a different mechanism of action, which may have subsequent benefit for the patient. So those are really the four larger buckets of therapies that I think about when I'm talking to patients in clinic.

So the introduction of JAK inhibitors has really changed how we treat our patients. Now in the last five years we now have three additional drugs that are approved, which we are thrilled about, in the community, mostly because these are oral agents that are well tolerated. And now we can keep treating our patients, myelofibrosis when the first drug runs out of gusto.

So Fedratinib is available as another alternative drug selling, should there be progression? Some people use that frontline. I tend to use that after suboptimal responses to Ruxolitinib if there's no clinical trial available. So there's another drug that's available called Pacritinib that is marketed to patients with low platelets, giving us yet another option for when the myelofibrosis progresses.

And most recently, a drug that's been around for a while and the investigational setting, called Momelotinib. That drug is also a JAK inhibitor, but it also promotes maturation of red blood cells. And that offers us now another drug to use in especially in the cases of anemia or lower red blood cell count with myelofibrosis.

So we have so many more options than before. We've had improvements in our myeloablative and reduced intensity conditioning strategies to transplant patients as well. So I would say this is a better time to be diagnosed and living with myelofibrosis for us because we can actually do more for patients. And so it's a wonderful time for that.