Management of Adverse Events Related to Pacritinib in Myelofibrosis

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Ashwin Kishtagari, MD, assistant professor of medicine at Vanderbilt University Medical Center, discusses the adverse events (AEs) of pacritinib (Vonjo) for patients with primary myelofibrosis and low platelet counts.

The data from the PERSIST-1 and PERSIST-2 trials (NCT01773187, NCT02055781) demonstrated some notable toxicities in patients who received pacritinib. Kishtagari notes that a majority of patients reported diarrhea of grade 1 or 2. Gastrointestinal (GI) AEs are related to pacritinib inhibiting the FLT3 protein. He says this is usually well managed with loperamide (Imodium), and it is encouraging that no patients on the clinical trials needed to discontinue treatment because of diarrhea.

The drug also comes with a risk of bleeding, which can be dangerous if patients have a low platelet count and are on other drugs such as aspirin or anticoagulants. Kishtagari recommends anticoagulants be avoided before initiating pacritinib.

A prolonged QT interval is a known cardiac toxicity with pacritinib. Kishtagari advises patients to get repeat EKGs, particularly at the beginning of treatment, to determine whether their QT interval is too high to receive treatment, and then every 3 months to monitor for dose reduction or interruption if needed.

TRANSCRIPTION:

0:08 | The biggest AEs that were reported in the clinical trial, both in PERSIST-1 and PERSIST-2 [include]—one of the major AEs is the grade 1 or grade 2 diarrhea, which is reported in majority of patients, because pacritinib targets, along with the JAK2, it also inhibits a protein called FLT3, because of that, we expect some GI AEs. That is usually very well managed either by use of [loperamide] and one encouraging sign is [that] none, or very few patients in the clinical trial, discontinued the medication because of this AE profile, which shows that this medication is well tolerated and the AE profile that is experienced is manageable with the use of supportive care.

1:13 | Another thing I want to point out is there is a risk of bleeding. That is something to be mindful for, especially if the platelet count is low and the patient is on other medications which can put them at risk of bleeding, such as aspirin, as well as anticoagulation [drugs]; that needs to be monitored. Aspirin is allowed if the patient can tolerate but I think the important thing is anticoagulation is something to be addressed before initiating the patient on pacritinib. The third thing I watch out for these patients is monitoring the QTc interval by getting repeat EKGs, especially first at the beginning of initiation of treatment, and then subsequently every 3 months.