Myelofibrosis: Dosing JAK Inhibitors and Managing Adverse Events
Continuing their focus on optimizing JAK inhibitor therapy in myelofibrosis, panelists highlight dosing and adverse event management strategies.
Transcript:
John O. Mascarenhas, MD: Give us a sense in a patient like this: Do you ease them into pacritinib? Do you use the full dose? How are you following them? What are the expectations?
Kristen M. Pettit, MD: Yeah, I think it’s tough, and it’s evolving how we do this as well. Personally, [I think] it depends on a case-by-case basis. He’s already on a low dose of ruxolitinib. If he were on like ruxolitinib 20 mg [twice daily], I would consider a taper or maybe a steroid overlap or something like that because of that risk of the JAK inhibitor rebound as you’re switching from one agent to the other. He’s on such a baby dose of a JAK inhibitor right now, [so] I think in his situation, I would just switch him right over from ruxolitinib to pacritinib.
John O. Mascarenhas, MD: And at the full dose?
Kristen M. Pettit, MD: Yes, at the full dose. For pacritinib, that’s one of the benefits of pacritinib, that regardless of the platelet count, being able to start the full dose of 200 mg [twice daily and] hopefully maximizing that JAK2 inhibition that you’re getting into somebody because you don’t have the JAK1 inhibition that’s going to lower their platelet count more.
John O. Mascarenhas, MD: How closely do you follow someone when you’re transitioning them from [ruxolitinib] to [pacritinib]?
Kristen M. Pettit, MD: I follow [several things] pretty closely, symptom burden, spleen size worsening, any toxicities from the drug, cytopenias, all those kinds of things [that are] changing. I typically monitor CBCs [complete blood cell counts] depending on the situation. His platelet count is getting low, so I’d probably check his platelet count, his CBC, maybe once a week, maybe every other week, whatever was most feasible to him, and follow up with him clinically within usually 1 to 2 weeks of starting the drug. I think one of the things with the pacritinib to keep in mind is that the toxicity profile is a little bit different from it is with ruxolitinib. There are some things that in patients with myelofibrosis, historically, we’re not necessarily accustomed to thinking about proactively, that we need to think about proactively with some of the newer agents like fedratinib or pacritinib. The main thing is GI [gastrointestinal] toxicities. So diarrhea is very common early on; nausea and vomiting can happen early on as well. Those are things that I generally tell patients to expect, and then if they don’t happen, we’ll be happy. It’s better to be proactive, expect it, and be prepared for it rather than to be surprised by it, because I think it’s harder to get on top of it once it’s already developed. I, in advance, make sure patients have loperamide [Imodium] on hand at home. I often make sure they have an antiemetic, as well, or are at least easily able to get an antiemetic from our clinic if they need it once they start the agent. The good news is that these GI toxicities with pacritinib tend to get better over time, not worse. They tend to not be long-lived, and they tend to be things that occur within the first couple of weeks and then improve over time. I think if we’re proactive about it on top of it, there are things that we can get through without too much difficulty in the first couple of weeks.
John O. Mascarenhas, MD: Any concern about vitamin deficiency with pacritinib?
Kristen M. Pettit, MD: We’ve certainly seen that with fedratinib, or we have concerns about that with fedratinib. Fedratinib has a black box warning for Wernicke encephalopathy, the vitamin B1 or thiamine deficiency, which can occur specifically in patients with worse GI toxicities that aren’t appropriately managed. That hasn’t been seen or reported to date with pacritinib. Significant diarrhea or nausea is not fun for a lot of different reasons, even if it falls in the grade 1 or grade 2 category. I don’t particularly check vitamin levels, but I am very aggressive about preventing and managing the GI toxicities.
John O. Mascarenhas, MD: Andrew, in Florida, you have a reputation of being a myelofibrosis cowboy, and I’m curious, with ruxolitinib and low platelets, what is your comfort level in terms of thrombocytopenia and dosing [ruxolitinib]?
Andrew T. Kuykendall, MD: It depends on what other options you have. Before pacritinib was out there, we did a lot of trying to limp people along on ruxolitinib to try to make sure that we keep them on a JAK inhibitor. A lot of it depends on what you’re aiming for with the treatment. I think that if patients are on ruxolitinib and they are on a substantial dose, they’re getting benefit, they’re able to keep their spleen volume in check, their symptoms in check, and their platelets are running at 50 consistently or maybe 40 consistently—those aren’t patients I’m necessarily pulling directly off and switching to pacritinib. That’s a different patient from the one [with a lot more volatile] platelets. Where you’re putting them on ruxolitinib and immediately they’re dropping down, you’re dose reducing, they go back up, you put them back to a dose, and they’re dropping back down again. Those are patients [in whom] certainly switching to pacritinib could do that, and perhaps that practice will change. Those patients where we’ve gotten into a comfort zone are ones who probably got to that comfort zone out of necessity because we didn’t have alternative agents and now we feel comfortable there with them. With additional agents, we may make that switch earlier before going through those trials and tribulations to get them there. I think it’s an evolving target, but it comes down to: What’s your kind of comfort level monitoring that patient? How often are they able to get labs checked? How close are they to your center? Certainly, in Florida, we’re responsible for treating the entire state, so we we’re the main center. I think in New York, [New York], you guys have 5 or 7 … specialists, so you’re not responsible for as much. I think for that, you realize you’re going to have people who are going to be on the outskirts who are not going to have as much access to labs. You must be more careful with those folks; you have to talk to them and understand their local oncologists and their ability to be monitored appropriately.
Transcript edited for clarity.
