A discussion on when to switch a patient with myelofibrosis to a new JAK inhibitor treatment, and possible strategies for transitioning.
John Mascarenhas, MD: Srdan, in this particular case, let’s say you were inclined to switch therapy. Let’s say that the platelet count was 40,000 per mm3 and you were looking to improve the spleen and symptom burden. What’s the best approach to switching from one JAK inhibitor to the next?
Srdan Verstovsek, MD, PhD: This is certainly what you were describing worsening. The platelets go down, and things are getting out of hand. But even if the platelet stays at 68,000 per mm3 and the hemoglobin is 7.4 g/dL, if the spleen starts growing and the patient has symptoms, the symptom control and spleen are worsening. The numbers are low already. It’s time to change. In that case, you’d choose another agent.
In this [situation], for the first case, it might be fine to choose a nonmyelosuppressive JAK inhibitor. Do you need to have a platelet count of 47,000 per mm3? Or is 68,000 per mm3 low enough to consider pacritinib? I’d say that’s low enough in the second-line setting. I’d perhaps change from ruxolitinib to pacritinib because the numbers are low and I don’t want them to get lower. I want them to stay the same. I don’t want the hemoglobin to get lower. I want the hemoglobin to possibly improve. I want to control the spleen and symptoms, so I’d strongly consider pacritinib in this setting, despite the fact that the platelets aren’t below 50,000 per mm3. I’ll argue with the payers about that particular aspect.
How do I change from one to the other? It might be prudent to taper the ruxolitinib slowly. For example, if the patient is still on 10 mg twice a day, to go to 5 mg twice a day for 10 days, and maybe even 5 mg daily for a week, or a week of each while we’re getting the pacritinib. Sometimes [it’s smart to] overlap between the 2 if it’s possible for a couple of weeks to prevent any possible rebound in the symptoms from sudden withdrawal of ruxolitinib. Tapering over to another drug would make sense.
John Mascarenhas, MD: Aaron, keeping in line with this theme of the second-line setting and switching patients from one JAK inhibitor to the next, can you give us some insight in the most recent update to the NCCN [National Comprehensive Cancer Network] Guidelines as it relates to pacritinib as a second-line agent, platelet requirements, and the whole concept of line-agnostic therapy?
Aaron Gerds, MD: That’s the real challenge here. Srdan, you’re talking about that case, and the thing I struggle with is whether it’s the drug or the disease or both and how you attribute that. You have a patient who has relatively preserved counts but is pretty symptomatic and has a big spleen. You put them on a drug that makes them feel a lot better, with a better quality of life, and then on the back end you’re dealing with this consequence of thrombocytopenia and anemia. If it’s an adverse effect of the drug, then changing to a different drug would make sense. But if it’s disease progression of some variety to a more cytopenic phase of their disease, then that may not be the case, and you may have to do some more supportive agents. That’s the part I always struggle with regarding these types of scenarios, where they’re better overall but their counts are worse.
In the guidelines, it’s hard to capture that as well. What’s from drug and what’s from disease? That’s tough to quantify and put down on paper. With pacritinib in the second-line setting, we add that in the NCCN Guidelines. It sometimes has been referred to as line-agnostic therapy, meaning that it could be used at any point, whether it’s in the first, second, or third line, now that we have 3 approved JAK inhibitors for myelofibrosis. Certainly, the challenge was quickly getting pacritinib into the guidelines.
As we go forward with different revisions of the guidelines, we can refine that based on additional analyses that come out that we can add into the guidelines and different practice experiences that we can weave into the guidelines. That’s the beauty of guidelines. They’re somewhat of a living document, particularly the NCCN Guidelines, which separates it from the more rigorous, McMaster style of critical review and laborious appraisal of the data. The NCCN tends to be more of a living document over time, which is nice, and we can update things rapidly as more information comes in.
With the NCCN, the main focus was trying to get as much access and leverage to get access to these medications as we can. As we’ve talked before, there are data for pacritinib in the frontline setting as well as data for pacritinib in the second and third line after another prior JAK inhibitor. We wanted to keep it as open as possible. The challenge with that has been that there’s been ruxolitinib for so long and ruxolitinib by itself for so long, and we’ve learned how to stretch it using 5 mg twice a day and other maneuvers, including adding on anti-anemia agents. [The focus has been on] how we can stretch the ruxolitinib out further. But now that we have these other agents, the challenge is: how do we rewrite the guidelines to focus a little more on when we can jump in with a new JAK inhibitor? That has been the challenge with developing the guidelines now that pacritinib is approved.
Transcript edited for clarity.