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FAQs: MPNs Emerging Data
Myeloid Malignancies Clinical Advances Journal Club on Emerging Data for MPNs: Answers to Frequently Asked Questions

Released: July 18, 2024

Expiration: July 17, 2025

Courtney DiNardo
Courtney DiNardo, MD, MSCE
Brady L. Stein
Brady L. Stein, MD, MHS
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Key Takeaways
  • According to experts, there is no specific age restriction for ropeginterferon alfa use, but patients with severe autoimmune disease and uncontrolled depression/anxiety may not be appropriate candidates for this therapy. 
  • In patients with myelofibrosis, multiple JAK inhibitors (ruxolitinib, pacritinib, fedratinib, and momelotinib) are available as options for disease control; momelotinib or pacritinib are a particularly good option for patients with anemia (both) and thrombocytopenia (pacritinib).

Assessing and integrating new clinical data for individualized care of patients with myeloproliferative neoplasms (MPNs) has increasingly become more important with the release of clinical trial data updates, real-world reports, and positive results from phase III clinical trials. In this commentary, we share answers to frequently asked questions posed by a live audience of healthcare professionals on key emerging new data for MPNs presented at the 2024 ASCO annual meeting and the 2024 EHA congress, including our takeaways for practitioners looking to stay up-to-date.

Should we switch patients from hydroxyurea to ropeginterferon alfa and who would you not start on ropeginterferon alfa for polycythemia vera (PV)? 

Brady L. Stein, MD, MHS:
Historically, we have used interferons for younger patients. We know that the ropeginterferon alfa trials also included older patients as well. In my practice, I have patients who are older than 60 or 65 who are tolerating the medication well. I am not convinced there is an age restriction for the use of this medication. I think the patients we would not want to start on ropeginterferon alfa would be those who have more classical contraindications to interferons, for example severe autoimmune disease or uncontrolled depression or anxiety. Those are 2 considerations that might make me a little reluctant to use an interferon for PV.

Would I switch all patients? Not necessarily. There is some selection involved, but if I were to have a discussion with a newly diagnosed patient that needs treatment I would bring up both agents and introduce the concept of molecular response. I think that might be useful if we can potentially show a patient a clinical outcome of meaningful interest if there is a molecular response. 

At what level of thrombocytosis with no reactive cause do you need to start treatment in a patient with essential thrombocythemia? 

Brady L. Stein, MD, MHS:
The platelet count predicts for bleeding, but it is a poor predictor for thrombosis. If we think about the use of cytoreduction, it is more based on vascular risk and symptoms. By contrast, if we are strictly looking at a platelet count, many of us will use 1.5 million to inform start of treatment even in the absence of higher-risk features or symptoms.

Regarding dosing of momelotinib and pacritinib in patients with myelofibrosis (MF), do you increase incrementally or dose reduce? 

Brady L. Stein, MD, MHS:
For pacritinib, I try to give the full dose based on the prescribing information.  With pacritinib, it should be noted that the platelet count may not improve but it should not significantly worsen so I would not use that as limiting my dose.

For momelotinib, I would go by the prescribing information as well. The best outcome for treating anemia is probably achieved at the standard dose, which is 200 mg daily. In other words, I would start with the standard dose rather than starting low and incrementally increasing the dose. 

Because we know that anemia and thrombocytopenia are adverse events with ruxolitinib, one might argue that for a patient with MF and severe anemia, if you are planning to use ruxolitinib, you may start dosing incrementally. A phase II clinical trial supported starting at 10 mg twice daily and increasing based on tolerance and many of us have done that.   

Have you seen patients who do not respond at all to newer agents for MF?

Brady L. Stein, MD, MHS:
Absolutely. Unfortunately, you can have a patient who might be refractory to treatment. I think the question of how long to try out the therapy before you stop treatment is a great one. In patients receiving ruxolitinib you can expect responses very early. After a few weeks to a month, you can start to see relief of inflammation and improvement in spleen size. By contrast, and based on historical data, we would give this treatment for 3 to 6 months and if we saw nothing happening, we would stop. For newer agents, it is my impression that the response takes longer. I have not seen early responses as with ruxolitinib, and the patient and hematologist may not see responses for a few months.

Can patients use either imetelstat or luspatercept for myelofibrosis-related anemia? What do you recommend? 

Brady L. Stein, MD, MHS:
Both imetelstat and luspatercept have been investigated in clinical trials but are not presently FDA approved for use in the management of MF-associated anemia. Previous reports suggested a potential signal for prolonged survival with imetelstat in patients with high-risk MF. In this setting, we know cytopenias can be a challenge. For this reason, imetelstat is not something we can use in clinical practice as it is not yet FDA approved. Looking at luspatercept, which is also not FDA approved for MF-related anemia, there has been a signal that perhaps it can offset some of the anemia arising from ruxolitinib use. Again, luspatercept is not FDA approved in this setting, but I have heard anecdotally that it has been used in clinical practice by colleagues. I think the responses are quite modest and I may consider other agents (such as momelotinib or pacritinib) that might be more effective for the treatment of anemia in MF. 

Courtney DiNardo, MD, MSCE:
Our institution has not used imetelstat as much. I have also heard from other colleagues and collaborators that what they are most impressed by with imetelstat is the response rate of approximately 40%, which is similar in many ways to erythroid stimulating agents and luspatercept. In those patients that respond to imetelstat, you can see a very dramatic improvement in hemoglobin which tends to be durable.   

Your Thoughts?
What are your thoughts or questions on the emerging data for patients with MPNs? Answer the polling question and join the conversation by leaving a comment. Also, visit the program page to view an on-demand webcast from the live event, download the associated slides, read other clinical commentaries, or listen to podcasts on emerging data for MDS, AML, and MPNs.

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