James K. McCloskey II, MD: Geeny, could you talk to us about the current FDA-approved drugs in this disease space and how they work in patients with myelofibrosis?

Geeny Lee, PharmD: We now have 3 medications that target the JAK pathway. And this JAK-STAT signaling pathway is important in the pathophysiology of myelofibrosis since its activation really leads to increased levels of proinflammatory cytokines that lead to various symptoms that we see in our patients with myelofibrosis. The first FDA-approved medication in this class is ruxolitinib. It was initially approved for myelofibrosis in 2011. And since then, it has gained several additional indications over the past decade in other diseases like polycythemia vera and acute and chronic graft-versus-host disease. But specifically, within the myelofibrosis space, ruxolitinib is approved for patients with intermediate or high-risk myelofibrosis, including primary as well as post polycythemia vera and … post essential thrombocythemia secondary myelofibrosis. Ruxolitinib is a kinase inhibitor that inhibits both JAK1 and JAK2, ultimately leading to decreased circulating inflammatory cytokines that cause a lot of symptoms in our patients with myelofibrosis. The second medication that was approved in this class is fedratinib. This medication was approved in August 2019 for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. As for its mechanism, it’s a kinase inhibitor that selectively inhibits JAK2 over others. So slightly different. And then lastly, the most recent medication to be approved in this class of JAK inhibitors is pacritinib. And this was approved February 28, 2022, for the treatment of adult patients with intermediate or high-risk, primary or secondary myelofibrosis with a platelet count of less than 50,000 under FDA’s accelerated approval program. And pacritinib is also a specific JAK2 inhibitor, but it also inhibits ACVR1, which is a little bit unique. And kind of piggybacking up your previous conversation, Dr McCloskey, what … is the role of an allogeneic transplant in our patients with myelofibrosis?

James K. McCloskey II, MD: That’s a great question. And it is a really hard question to answer because transplant is a very personal decision from a patient perspective. The easy answer is that [patients with] intermediate-2 and high-risk myelofibrosis who are fit and eligible for transplant and amenable transplant should be considered very closely for an allogeneic stem cell transplant. I think that our center particularly is fairly aggressive in this. Admittedly, there are conflicting data series and publications regarding the benefit in patients with myelofibrosis. I think what’s without question is that if we find the appropriate patient at the right time … these are patients who benefit from an allogeneic transplant. At Hackensack, our goal is to work with the transplant team early to really determine what are their options and what’s the optimal time to take that person to transplant.

Again, I think that many patients with this disease might be elderly, they might have other comorbidities that would preclude a transplant, and they may decide when they hear all of their options … that they don’t want to do it. So irrespective of the timing and the decision to go to transplant, we continue to work with the patient to optimize their disease management. Because we certainly know that taking them to transplant in a state where the spleen is better controlled, where we’ve preserved their nutritional status, where we’ve preserved their quality of life, their mobility, their functionality, is going to help them do better whether they get the transplant or not. I think that transplanters probably have more of a perspective on … the ins and outs of transplant and maybe which transplants would be preferred for these [patients]. But as I said, this is something we’re usually coordinating, but the most important thing … is that patients with myelofibrosis should be seen by a transplanter, and then once they’ve seen the transplant team, it’s usually … an ongoing conversation with the oncologist, the patient and the transplanter about when it’s going to be right for them and the pros and cons specific to their case.

Transcript is AI-generated and edited for clarity and readability.