Targeted Treatments for Myeloproliferative Neoplasms - Episode 1

Overview of Myeloproliferative Neoplasms

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A comprehensive overview of myeloproliferative neoplasms followed by insight on the differences between essential thrombocytopenia, polycythemia vera, and myelofibrosis.

Transcript:

Rami S. Komrojki, MD: Hello, and thank you for joining this Targeted Oncology® discussion titled Targeted Treatments for Myeloproliferative Neoplasms. I'm Rami Komrojki, Vice Chair of the Malignant Hematology Department at Moffitt Cancer Center, Tampa, Florida. I'm joined today by my esteemed and dear colleague and friend, Dr Pankit Vachhani, who I'd like to introduce himself as well.

Pankit Vachhani, MD:Thank you, Dr Komrojki. I'm Pankit Vachhani, I'm a leukemia physician at the University of Alabama at Birmingham. My clinical and research interests are in myeloid malignancies, including myeloproliferative neoplasms. I lead a leukemia BMT working group and direct our clinical research unit. I'm delighted to join, Dr Komrojki.

Rami S. Komrojki, MD: Thank you, a pleasure to have you. Today in precedent medicine in oncology, we will talk about treatment options for patients with myeloproliferative neoplasms, this is a field evolving where the precision of medicine or importance of molecular annotation is becoming very important, and how to select appropriate treatment based on patient and disease-related factors. Let me start by providing an overview of myeloproliferative neoplasms. Our audience knows myeloproliferative neoplasms are a group of chronic myeloid neoplasms, those are all stem cell disorders, they are characterized by proliferative features, presentations with constitutional symptoms, renomegaly, as well as cytopenia sometimes. The classic in myeloproliferative neoplasms include CMN which is a disease we always must exclude or rule out because of phase 3 of the availability of treatment options. Then we typically of think of essential thrombocythemia, polycythemia vera, and myelofibrosis, and a bag of unclassified diseases, less commonly chronic neutrophilic leukemia, and chronic eosinophilic leukemia. Those diseases typically happen in the ages 60-70, each of them happens in 1 per 100,000 roughly, but it's important to recognize that they have a symptomatic burden on the patient and consequences of transforming to acute myeloid leukemia, most of them, eventually, will impact the survival of patients. And unique to myeloproliferative neoplasms is obviously the thrombotic aspect of those diseases where the risk of thrombotic events is increased. That typically could be life-threatening in the first 10 years of the course of the disease. And when we think of those myeloproliferative diseases, obviously, myelofibrosis particularly is probably one of the most symptomatic and the burden of the disease on the patient's quality of life and daily activities is very important. Having said that, I probably will ask now Dr Vacchani to give us his view on describing the similarities and differences between the most common types we deal with, essential thrombocythemia, polycythemia vera and myelofibrosis.

Pankit Vachhani, MD: Thank you, Dr Komrojki. You stated beautifully there are many similarities between these 3 classical Philadelphia chromosome-negative MPNs in that they are all driven by the JAK/STAT pathway activation. They also share a very similar profile of mutations, and I'm sure we'll talk about this in a little bit, but these are the JAK2, CALR, and MPL mutations, for example. Cytosis or elevated blood counts, be that white blood count, hemoglobin, hematocrit values, or red cell mass, as well as platelet counts can be elevated. Maybe in some cases down the line these blood counts can go down, or occasionally, even at the time of presentation. But in general, elevated blood counts or cytosis is another similarity. Spleen enlargement and even liver enlargement can be frequently found in these patients. These patients can have a high symptom burden and an overall tendency towards increased fibrosis and leukemic transformation. While these are the similarities, the differences are along these very same points, in the sense that the 3 MPNs, classical MPNs, present somewhat differently. For example, polycythemia vera, presents with elevated hematocrit, hemoglobin, red blood cell mass, but in addition, can also have elevated white blood count and platelets. On the other hand, for essential thrombocythemia, the most prominent feature is platelet count elevation or thrombocythemia. Yes, some patients can also come with white blood count elevation there. On the other hand, myelofibrosis usually comes with an entire range of possibilities, now that could be a cytopenic presentation for a small fraction of patients, or a more proliferative phenotype for a wide variety of patients which can, over time, change and become cytopenic down the line. In addition, myelofibrosis patients come with a more prominent splenomegaly, unlike, let's say, essential thrombocythemia. The thrombotic risk is also different, the patients with PV have more thrombotic risk compared to ET or MF, for example. And the leukemic transformation rates similarly vary as well, for essential thrombocythemia, it is less than 5% per decade, for PV, it is somewhere around 5-10% per decade, and on the other hand for primary myelofibrosis, it is around 10-20%, a higher rate over there. And PV and ET patients can have their survival measured in decades, while those for myelofibrosis varies usually from a range of a couple of years to more. In terms of how they present, besides the points that we all spoke about, in particular for PV and ET, many of our patients get found to have these blood abnormalities on routine labs, whether that be prior to some procedure or annual examination. But there is also a fraction of patients who are found to have these conditions during or around the time of a thrombohemorrhagic episode, let's say, stroke or myocardial infarction. On the other hand, for myelofibrosis patients, they can have a high burden of symptoms, they can be anemic and have symptoms from that, spleen can be enlarged, and patients may have spleen-related pain or discomfort, or appetite changes or early satiety, and these may be the driving factors that brought them for evaluation.

Transcript edited for clarity.