Pacritinib in Myelofibrosis: Adverse Event Management and Dosing

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Shared insight on the safety profile of pacritinib and how best to mitigate or manage adverse events when they occur in patients with myelofibrosis.

Transcript:

James K. McCloskey II, MD: So I think that we talked a lot about the efficacy end points for pacritinib. Geeny, can you tell us about some of the toxicities and some of the things that maybe we should watch out for in patients who are starting the drug?

Geeny Lee, PharmD: Some adverse events that we can see with pacritinib include diarrhea, prolonged QT interval, peripheral edema, thrombocytopenia, and hemorrhage, and some I will elaborate [upon]. The first adverse event that I really want to discuss is diarrhea. It is really the most common [adverse] effect that’s seen with…pacritinib. So, in clinical trials, luckily [they] were mostly low grade and led to very few discontinuations, but it was seen in about half the patients. So it is definitely important to counsel patients on the [adverse] effect. For low grades, grade 1 or 2 diarrhea, we may be able to just continue treatment while utilizing antidiarrheal medication like loperamide over the counter and encourage patients to stay hydrated, but for any diarrhea that is grade 3 or higher, we may have to hold treatment until resolution. And in case there’s a recurrence, we may also have to adjust the dose of pacritinib when we resume the treatment on the patient.

And the second that I want to highlight is that pacritinib can also lead to worsening thrombocytopenia. For any significant worsening that lasts more than a week, we may have to hold treatment and resume it [at] half the dose when it’s resolved. Along with that, pacritinib can also increase [a] patient’s risk for hemorrhage, and for this we want to hold treatment for any bleeding that requires intervention. And depending on the severity and whether this recurs or not, we may have to really adjust the dose when resuming treatment. It’s also important to remember that we do need to hold pacritinib for at least 7 days prior to any plans surgical or invasive procedures. The last adverse event that I want to highlight is prolonged QT interval. And we should monitor with an EKG before starting treatment and then periodically thereafter. We do need to avoid starting the treatment in patients whose baseline QTc is greater than 480 milliseconds. And during treatment, if we see any QTc that goes above 500 or if you see an increase of greater than 60 from baseline, we have to hold treatment until resolution. So it is very important to get the baseline as well so we can see the change. And based on how long it takes for prolonged QTc interval to resolve, we may have to adjust the dose when we resume their treatment.

And we also want to keep an eye on their electrolytes, especially their potassium, before starting and during treatment and repeat as needed. And that can certainly help us manage the [adverse] effects as well. I think, overall, it’s important not only to educate our patients on what to watch out for but also encourage them to communicate with us [about] any new changes that they are noticing. For a lot of these [adverse] effects, they can be managed with supportive care, temporarily withholding, and adjusting the doses. So we want to make sure that they know to reach out to us with any questions or concerns so we can really address them earlier on. And with that, maybe, Danielle, would you be able to review the dosing of pacritinib in this case?

Danielle E. Marcotulli, APN: In this case, JM was started on full-dose pacritinib 200 mg BID, I think previously even you saw it when we first started him on Jakafi, we could only dose him at 10 mg BID [twice a day], which was not the full dose, and you’re not getting the effect of what that drug can really do for you. So even despite all of…his worsening cytopenias, we’re able to dose pacritinib at full dose so the patient can get the maximal benefits from that drug, which is very important because previously we’ve struggled a lot with increasing dose due to cytopenias. Typically, we are giving the full dose up front, as Geeny said, dose reducing as necessary, but right away when we’re starting new patients on pacritinib, we’re starting at the 200 [mg] BID, not worrying about the cytopenias and trying to see if that patient can get the best effect from the medication.

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

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