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Contemporary Myelofibrosis Care
Contemporary Myelofibrosis Care: Experts Answer Your Questions

Released: May 18, 2023

Prithviraj Bose
Prithviraj Bose, MD
Stephen Oh
Stephen Oh, MD, PhD
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Key Takeaways
  • JAK inhibitors can provide rapid symptomatic relief in patients with myelofibrosis and progressive constitutional symptoms.
  • Counsel patients about potential gastrointestinal adverse events associated with pacritinib and fedratinib and strategies to manage them.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow scar tissue. Treatment modalities include stem cell transplant, which is potentially curative, or drug therapy with JAK inhibitors, which can help control symptoms. This commentary provides expert answers to questions asked at several workshops on MF care in April 2023 across the United States.

How quickly is it expected for patients to have symptomatic relief with ruxolitinib or other JAK2 inhibitors?

Stephen Oh, MD, PhD:
The discovery of alterations in the JAK/STAT pathway contributing to MF pathophysiology has led to development of JAK inhibitors in treatment. The place in therapy for JAK inhibitors is in overt MF for transplant-ineligible patients with progressive constitutional symptoms and organomegaly. In practice, symptomatic relief is variable with individual patients in terms of the timing of symptom response, but often relief occurs relatively quickly. Within a few weeks, patients will notice some degree of improvement in symptoms such as night sweats, poor appetite, poor energy, abdominal discomfort, or early satiety. The enlarged spleen creates a feeling of fullness, which can cause discomfort during eating. In general, maximal response occurs within 6 months, but overt response happens relatively quickly with ruxolitinib, fedratinib, or pacritinib.

What if your patient already had a transplant and had disease progression? Would you consider a JAK inhibitor at that point?

Prithviraj Bose, MD:
When there is MF disease progression in a patient who previously has undergone a transplant, it can be approached similarly to how a previously untreated patient would be managed. In the presence of an enlarged spleen or other disease symptoms, JAK inhibitor therapy would be the therapy of choice. If the patient is presenting with cytopenias in addition to splenomegaly and/or symptoms, then it is important to provide supportive treatments to help with the cytopenias, together with JAK inhibition, and/or use a JAK inhibitor that may improve cytopenias. If cytopenias are the only problem, JAK inhibition may not be warranted. Overall, the management approach will be based on the specific clinical needs of the patient.

If you have a patient who is transfusion dependent and has platelets >50 x 109/L, which agent would you start?

Prithviraj Bose, MD:
For patients presenting with platelets of 50-100 x 109/L, ruxolitinib has been the standard option, although I typically dose it at 10 mg twice daily, and not 5 mg twice daily, as per the US label, given the findings from the EXPAND study. In the COMFORT trials, development of anemia did not affect response to ruxolitinib or survival, and baseline anemia is not a contraindication to ruxolitinib use. Fedratinib can be employed at full dose (400 mg in this population) based on subset analyses from the JAKARTA trials that showed similar efficacy irrespective of baseline platelets. Patients with platelets ≤100 x 109/L were enrolled on the PERSIST-2 trial of pacritinib; platelets were ≤50 x 109/L in 42% of the patients receiving 200 mg twice daily. There also are encouraging anemia and transfusion independence data with pacritinib from PERSIST-2. I would consider initiating pacritinib in such a patient, although its use in patients with platelets ≥50 x 109/L is outside the labeled indication.

How quickly is it expected for diarrhea to resolve with pacritinib and fedratinib?

Prithviraj Bose, MD:
In addition to JAK2, pacritinib and fedratinib have other targets, including FLT3. It is thought that the FLT3 inhibition may be contributing to gastrointestinal adverse events. With pacritinib, the diarrhea is generally at its maximum within the first 8 weeks. It is important to aggressively preempt it by educating the patient to have loperamide available and take it at the first onset of diarrhea. Patients are less likely to experience nausea with pacritinib than fedratinib; it is my impression that there is more gastrointestinal toxicity with fedratinib. With fedratinib, nausea, vomiting, and diarrhea are at their peak within the first 4 weeks and then gradually taper off. Ensure that your patient receiving fedratinib has ondansetron available. Of course, always check baseline thiamine levels and monitor them while patients are receiving fedratinib. Many healthcare professionals routinely supplement thiamine in patients receiving fedratinib.

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What are your thoughts and questions on current JAK inhibitor therapy and novel management approaches for patients with MF? Please answer the polling question and join the conversation by posting a comment in the discussion section.

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