Optimal Selection and Sequencing of Therapy in Patients With Myelofibrosis

Transcript:

Geeny Lee, PharmD: So, Danielle, we’ve talked a lot about drugs. I know I’ve been tossing around a lot of numbers here. Can you talk…about how this comes into the clinic, how it comes to life? How do we decide on a treatment and what are some of the challenges that we face…? And also…when would you consider a clinical trial?

Danielle E. Marcotulli, APN: So I think, typically, when we’re seeing patients, we kind of always have clinical trial in the back of our mind, even upon initial diagnosis, progression. We’re constantly screening these patients to see if we have a good option for them. When choosing therapy, specifically, I think you’re looking [at, is] that patient, more of that, cytopenic, myelofibrosis, are they more proliferative, depending on their counts, can we give them Jakafi without causing major cytopenias, or did they come to us already very cytopenic and may benefit from [a] more pacritinib-type drug? And I think it’s really important to assess [a] patient’s symptoms because…I think there’s such a wide variety of symptoms with myelofibrosis patients. They may come and not really have many symptoms, and then other people are coming, and they have absolutely every symptom. So I think it’s important to talk to the patient and figure out what drug kind of fits them best. As far as transplant goes, I think it’s so important to get that conversation started in the very beginning when we’re meeting them, because so often we’re seeing patients and you have a window to transplant a patient, and sometimes by the time we’re seeing them in our office, they are getting too sick for transplant or too old for transplant. So, I think it’s really important to at least work them up, especially if they’re an intermediate-2 or high-risk patient. Get them hooked up with your transplant team, see what their options are, because transplant can’t happen overnight. This takes many months to plan. And knowing what our options are up front can help us definitely best manage that patient and then get them over to transplant if appropriate. Dr McCloskey, how do you approach sequencing therapies for patients with myelofibrosis with our currently approved agents?

James K. McCloskey II, MD: I think the first thing and most important thing is that we’re thinking about sequencing. I think we are finding that many times we’re…stuck in a rut because we’ve gone so long with just the same tools and the tool basket that there can be a tendency to really forget about the other options or maybe not appreciate the value of controlling some of these parameters we talked about. So the first thing is that we are constantly looking for treatment failure. It is incredibly important that you examine your patients every time they’re there, that you palpate the spleen. We have now routinely implemented [that all patients get] an ultrasound at least once a year. And I guess for me, I think the first thing that I do, and I say this all the time, is I determine—we’re talking about ruxolitinib first line—what I expect that drug to do for me. If it’s supposed to be controlling symptoms, then I’m monitoring the symptoms while I’m watching for the spleen. If I am trying to control the spleen volume, [and] if it’s not doing for that for me, then I know I need to change.

Additionally, if I cannot keep the patient on an adequate dose, then I need to switch. Because with ruxolitinib, we know that spleen volume reduction is a dose-related phenomenon. And so I think that the first step is just recognizing we have those other options. And I think Danielle mentioned one of the… things that drives us, particularly in our clinic, is that we have all these trials. So we’re always trying to put patients on a trial. But I think that for me, I often am looking at that spleen volume reduction, and I often if I’m in a meeting and I am sitting in a room full of people, I have colleagues that will cite the value of spleen volume reduction in those patients, and the fact that, hey, if we can control the spleen volume, we improve survival. And I have colleagues who will [say], well, that is selection bias. And I totally agree. If we’re writing a paper, if we’re talking about our next clinical trial, yes, it is selective bias. But the fact is that we take care of a lot of patients. Danielle and I see many patients during the week, and it’s our response to care for them. And when that patient, when SM is in front of me, I don’t know whether or not she’ll be a responder. So I think it’s my job to offer her that opportunity to have a response. So that’s why we really think it’s so important to stay on top of the spleen, so we intervene early and sequence early when there’s treatment failure.

When we’re switching between agents, then it can be challenging. Remember that these patients can have a ruxolitinib withdrawal independent of which agent we’re talking about. So, usually I try to taper the ruxolitinib down and switch over to one of these other agents. If I’m having a patient who is particularly symptomatic, I may send that patient… home with some steroids to have on hand in case we see ruxolitinib withdrawal. I think, going back to momelotinib, that trial require[s] a washout, and I can remember patients who in fact didn’t make it on study because they just couldn’t be off the ruxolitinib. And so that’s the one thing I would say is important. Otherwise, I tend to switch between all these agents pretty quickly once I’ve tapered them down and watch them closely. I think as you switch over, keep in mind these drugs could have different behaviors for your patients. If you have an elderly frail patient, give them a call, check on them to make sure that they’re doing OK and [that] they’re not withdrawing at all.

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