Stephen Oh, MD, PhD, describes the factors that influence treatment selection in myelofibrosis, and then reviews sequencing strategies.
Stephen Oh, MD, PhD: With the updated data that we have available, including the presentations from this year's ASH [meeting], an obvious question is which therapy you would use and in what setting for which patient. For example, if we're talking about a cytopenic patient with platelets less than 100,000 or less than 50,000, plus or minus some degree of anemia, how do we decide which agent to use? This is something that continues to evolve. We currently have 3 approved JAK inhibitors: ruxolitinib, fedratinib, and pacritinib. We have historically utilized ruxolitinib as the first-line choice for all patients who meet criteria for ruxolitnib, which would be a platelet count of at least 50,000. And now with the approval of pacritinib, we have that specific category, platelets less than 50,000, where it would be an obvious choice to consider pacritinib.
But now that we have more data, this makes the choice a little more nuanced. Let's say we have a patient with a platelet count between 50,000 and 100,000. This is strictly speaking not in the label indication for pacritinib, but it may be a patient for whom ruxolitinib may be the initial treatment choice. But the likelihood of achieving a meaningful dose with that kind of platelet count to provide symptom and spleen benefit is not super high. And while the patient may be initially started on ruxolitnib, switching to pacritinib or another agent in that setting may be expected to some extent. That is something that more and more is a consideration. And then when you add into that the evolving understanding of anemia and its potential for improvement with some of these drugs, that also is an important consideration as well.
As far as sequencing these different drugs and how to use them and when to use them, currently and probably for the foreseeable future, ruxolitinib will continue to be the most common choice. That's partly based on familiarity and experience with over a decade now that this drug has been available. We know that it provides robust spleen and symptom benefit for many patients with myelofibrosis. But again, the field is evolving. We have said for many years that the mantra for treating patients with myelofibrosis is that we expect the hemoglobin to decrease. We expect anemia to get worse and the platelet count to go down. Despite that, ruxolitinib is still beneficial. That may be the case, but now we have other agents, including pacritinib, fedratinib, and maybe soon to be momelotinib that can be utilized as second-line agents or even potentially as first-line agents. Most patients will still be started on ruxolitinib initially, but all of these other agents will be options in particular when we're talking about cytopenias, in which case switching to one of these other agents may be advisable.
As far as choosing one of these other agents as first-line therapy, I mentioned earlier that pacritinib is indicated for patients with platelet counts less than 50,000. That seems straightforward. For other patients who have low counts overall, but perhaps not less than 50,000, I think you can potentially make the case that pacritinib is a relevant choice, whether it's in the first-line setting or after a relatively short period of treatment with ruxolitinib. And somewhat similarly, if momelotinib does get approved next summer, we'll find that it has a role in particular in patients with myelofibrosis with anemia, and there will be some overlap for sure in that group of patients for whom we think momelotinib and pacritinib may be reasonable choices, but also enough of a distinction that I think both drugs will be utilized frequently.
Transcript edited for clarity.