Recent updates to the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) – both types of myeloproliferative neoplasms (MPN) – are shifting the way that these patients are treated.
Specifically in the guidelines, the needs of patients who progress on these MPNs are addressed. Although many patients with PV or ET can be treated with phlebotomy and aspirin, physicians must be aware that there is a population who will progress, says Ruben A. Mesa, M.D.
“It is a big advance for these patients to finally have both the standardization, as well as the establishment of a standard of care with guidelines for therapy in the United States,” says Mesa. “I would say that their management in the past has sometimes been more heterogeneous than would be ideal.”
Additionally, the updated guidelines clarify the role of Jakafi (ruxolitinib), a JAK2 inhibitor used in the second-line setting for patients with PV.
In an interview with CURE
during the NCCN 12th Annual Congress on Hematologic Malignancies, Mesa, director, UT Health San Antonio Cancer Center, shed light on these recent updates in PV and ET, and discussed the proper therapeutic management of these diseases.
What are the important updates in PV and ET?
These are the inaugural guidelines for the management of PV and ET coming out of the NCCN this summer. I am very excited, as the MPN panel chair, to be able to bring these to providers in the United States and elsewhere who are managing these patients. We are trying to bring some uniformity—to set some standards in terms of care.
Diseases such as PV and ET are unique in many ways. They are malignancies, but they are very chronic malignancies. Patients have a very long survival, and some patients may even have near-normal survival. All of that said, the diseases can progress and can really inflict morbidity on patients afflicted through risk of thrombosis, risk of hemorrhage and risk of progression.
Fundamentally, the guidelines try to first establish risks for a given patient such as thrombosis and bleeding—the morbidities that are suffering from. Additionally, they should be mindful of risk of progression. In both sets of diseases, our primary goals are the avoidance of thrombosis and bleeding in a risk-based fashion. Irrespective of risk, individuals likely start on baby aspirin. For individuals with PV, we try to control the hematocrit through phlebotomy.
For individuals who have increasing risk, difficult-to-control symptoms, prior history of thrombosis or bleeding, or are over the age of 60, we then employ cytoreductive therapy. The exact selection of cytoreductive therapy are the “meat” of the guidelines regarding the difference between ET and PV.
Are there any particular challenges that are impeding physicians from properly managing these patients?
Managing patients with PV has been challenging because of the limited availability of agents. Practicing providers have primarily used hydroxyurea, a therapy not even really approved for PV, but is a non-specific cytoreductive therapy. A major limitation is that many patients who are on hydroxyurea don't have a great experience. They can have toxicities; or, what I find more commonly is that they have a partial response, but they don't tolerate a high enough dose of hydroxyurea to actually achieve the goals of adequately controlling the counts.
One of the important parts of our new NCCN guidelines is clarifying the role of Jakafi, a JAK2 inhibitor for PV. Interestingly it’s the only therapy for PV as a second-line therapy, and there is no FDA-approved frontline therapy. It has been quite helpful in patients who have failed hydroxyurea for control of hematocrit, and in individuals who are poorly tolerating phlebotomy by helping to control splenomegaly, and helping to control symptoms.
Are there any systemic therapies being investigated in the frontline setting?
In frontline therapy for PV, there is currently a series of phase 3 clinical trials looking at a comparison of hydroxyurea versus pegylated interferon. These initial studies have largely showed that pegylated interferon is helpful, but it is non-inferior to hydroxyurea. Therefore, they both have similar activity in controlling counts and diminishing the role of thrombosis and bleeding. Whether one is superior over the other in the long term is something we will need more data to know.
How do you think adhering to these guidelines and properly managing these patients will affect the overall treatment landscape going forward?
Going forward, we are going to be much more active in terms of treating these patients. Both ET and PV have largely been undertreated; people are either delayed in receiving treatment or receive inadequate treatment, in part, over fears of concerns with the toxicities linked with hydroxyurea. Jakafi is a clear advance for these patients, and there will be an important role for interferon in the management of these patients. There are also other things in the experimental phases of development.
Most of our paradigms, which have been quite conservative, really have been based on fear of hydroxyurea and once we get past that paradigm, we will manage these diseases more appropriately. It is true that they are not acute malignancies, such as an acute leukemia or a diffuse large B-cell lymphoma; however, they are not benign diseases. [PV and ET] have a progressive nature; they clearly can affect patients in a significant way and they can lead to significant morbidity and/or mortality.