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Challenges Remain in MPN Diagnosis and Drug Development

Caroline Seymour
Published: Monday, Sep 10, 2018

Andrew T. Kuykendall, MD

Andrew T. Kuykendall, MD

Drug development in myeloproliferative neoplasms (MPNs), specifically polycythemia vera (PV) and myelofibrosis, have both remained similar to their diagnosis: difficult, explained Andrew T. Kuykendall, MD.

Regarding therapeutic advances, the FDA approved ruxolitinib (Jakafi) for the treatment of patients with myelofibrosis and polycythemia vera in 2011 and 2014, respectively. However, researchers are diligently working to bring more novel agents to the field.

The JAK2/FLT3 inhibitor pacritinib, though put on a clinical hold in 2016, is back on trial. The agent is being tested in patients with primary or secondary myelofibrosis who did not benefit from ruxolitinib or were not eligible to receive the agent in the ongoing PAC203 study (NCT03165734). Though momelotinib has been explored, it has demonstrated mixed findings in clinical trials, Kuykendall explained.

“Trying to get additional agents on board especially for different phenotypes of [myelofibrosis] is where I see the field going,” said Kuykendall, an assistant member of Moffitt Cancer Center. “In PV, we need to make some strides in understanding how to better treat the disease overall. We also have to understand what it means when we decrease the JAK2-mutant allele burden.”

In an interview during the 2018 OncLive® State of the Science SummitTM on Hematologic Malignancies, Kuykendall discussed the presentation of these neoplasms, novel agents in development, and the overall outlook of these diseases.

OncLive®: How do these neoplasms typically present?

Kuykendall: The first challenge with diagnosing PV is ruling out primary PV from other causes that lead to erythrocytosis. The JAK mutation has been extremely helpful because it identifies patients who have this disease. The new World Health Organization criteria has relaxed the hemoglobin thresholds that we used to have, so that has allowed us to capture an increased volume of patients who otherwise weren't meeting the criteria.

The challenge has become how to differentiate PV from some of the other related MPNs. We typically like to do bone marrow biopsies. Those aren't always mandated but are in the vast majority of cases. They can be extremely helpful in differentiating PV from other related diseases that can present very similarly.

Myelofibrosis is a more difficult challenge. Myelofibrosis is largely diagnosed off the bone marrow biopsy. It can present in any number of ways with thrombocytosis, erythrocytosis, or leukocytosis. It can present with cytopenias and relatively normal blood counts, but a lot of symptoms and splenomegaly. It's different for every patient, and so we normally go based on the bone marrow morphology. Next-generation sequencing has helped us to some degree to identify driver mutations in addition to cooperating mutations that we know occur more often in these diseases.

How have novel agents impacted the field?

Ruxolitinib has had a huge impact across the MPN field. It's an intelligently designed drug that acts on the JAK-STAT pathway, which we know is hyperactive in all of these conditions. In myelofibrosis, it has probably made the biggest change in how we approach the disease. It’s allowed patients who are incredibly symptomatic to be resolved of their symptoms and go back to feeling normal. This wasn't previously possible. We're still trying to understand how much it's revolutionized the landscape as far as how it's improving transplant outcomes, why we're seeing survival benefits, etc.


View Conference Coverage
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TitleExpiration DateCME Credits
Clinical Interchange™: Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize OutcomesOct 31, 20182.0
Hematology Briefings™: Advancing Care and Improving Outcomes for Patients With Pyruvate Kinase DeficiencyOct 31, 20181.0
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