Transcript
Hello. I'm Ruben Mesa. I'm the Director of the Mays Cancer Center at UT Health San Antonio MD Anderson. I'm here, live, onsite, at the Great Debates & Updates in Hematologic Malignancies. I presented at this meeting a talk on aggressive cases of MPNs, or myeloproliferative neoplasms.
What do we mean by aggressive cases? First, there can be aggressive cases with essential thrombocythemia or polycythemia vera. They can be aggressive because they have a rapid tendency to progress, or they can be aggressive because of increased risk of thrombo or hemorrhagic complications.Patients that have very high platelet counts, patients that have recurring vascular events. We go through discussions on case scenarios with these.
In the end, the key is to recognize when patients have a bit more aggressive phenotype for bleeding or clotting.
One, we ask ourselves, "Do they have an additional risk factor, either a familial thrombophilia or an additional coagulopathy that we need to be mindful of, that's been undiagnosed?" Two, we need to be that much more stringent regarding our cytoreduction and really trying to optimize the control of the counts.
Another group that particularly are aggressive are those that have been previously splenectomized, either because of trauma or because of intentional therapy for myelofibrosis. This can be individuals with either ET, PV, or myelofibrosis, where then, frequently, control of the counts can be challenging.
In these settings, frequently, the need for combination therapies is required. Even if they're on ruxolitinib, which can be very helpful, they may well require additional hydroxyurea or anagrelide or interferon to adequately control the sort of hyperleukocytosis and hyperthrombocytosis that can occur in the setting of splenectomy.
Third, we cover the patients that have the progressive phenotype toward acute leukemia or blast phase. Those likely with a blast count of over 10% functionally act as if they have acute leukemia.
For them, we need to be particularly aggressive. We ask ourselves first, "Is there a curative path? Can we cytoreduce them to get into a sufficient degree of disease control to be able to then proceed to a stem cell transplant?" If not, we do increasingly have some targeted therapies that are available, either in clinical trials or off-label.
There has certainly been use of venetoclax in hypomethylating therapies. There's relatively limited data in MPNs, but there certainly is activity. There's the IDH1 and IDH2 inhibitors, either alone or in combination with ruxolitinib. There's currently clinical trials for this. It has been used off-label.The data is still forthcoming in that the initial clinical trials for approval did not include these agents.
We have the new formulations of the fixed ratio of anthracycline and AraC. Although we do not have specific MPN-related data, this may be a consideration particularly for patients that are being induced, that likely will then move on to a stem cell transplant.
Aggressive phenotypes can have a variety of different manifestations in patients with MPNs. Finally, I'd cover patients can rarely have, but it's important to know that they can have, non-hepato or splenic areas of extramedullary hematopoiesis.
Indeed, EMH can show up anywhere in the body, from a spinal cord compression to a lung mass to a lymph node. Key to be mindful of this, as well as know that these areas tend to be exceedingly radiosensitive if they're causing pain, symptoms, or immediate difficulties.
Many patients with MPNs fit your standard guidelines but be mindful there are patients that can be more aggressive and frequently will need combination therapies and frequently a team-based approach of all of the specialists involved discussing the cases. Thank you.
