Overview on Essential Thrombocythemia and Polycythemia Vera Management


Expert perspectives on the respective treatment landscapes of essential thrombocytopenia (ET) and polycythemia vera (PV) following the ASH 2022 Annual Meeting.


Naveen Pemmaraju, MD: Hello and welcome to this OncLive Peer Exchange® entitled “Recent Data and New Learnings in Myeloproliferative Neoplasms.” I’ll be your moderator. I’m Dr Naveen Pemmaraju, associate professor of leukemia at [The University of Texas] MD Anderson Cancer Center in Houston. Joining me today in this discussion are my great friends and colleagues, and I’ll ask them to each introduce themselves. I’ll start with Professor Ruben Mesa….

Ruben Mesa, MD: Naveen, I’m excited to be here. I’m Ruben Mesa. I’m the executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson.

Naveen Pemmaraju, MD: Great. And then Professor Mascarenhas.

John Mascarenhas, MD: I’m John Mascarenhas, I’m a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, and I appreciate the invitation to join you.

Naveen Pemmaraju, MD: Thank you so much. Professor Oh.

Stephen Oh, MD, PhD: Thank you. Happy to be here. I’m Stephen Oh from Washington University School of Medicine in St Louis, Missouri.

Naveen Pemmaraju, MD: And Professor Jeanne Palmer.

Jeanne M. Palmer, MD: Thank you very much for having me; it’s always a joy to be here. I am an associate professor of medicine at Mayo Clinic in [Phoenix,] Arizona.

Naveen Pemmaraju, MD: Thank you all for being here at this important educational opportunity. Let’s get started on our first topic. The first thing that I want to start out with in our MPN [myeloproliferative neoplasm] space is that of essential thrombocytosis. ET [essential thrombocythemia] is 1 of our 3 major MPNs. [As we learned] at the 2022 ASH [American Society of Hematology Annual Meeting & Exposition], and actually over the past year, there have been several novel agents in ET, but in general, the field has started to see some progress. Dr Mesa, I’d like to start with you. Can you talk about ET in general and some of the therapies that have come out, including the pegylated interferon, the LSD1 inhibitor, and even JAK [Janus kinase] inhibitors for the field of ET?

Ruben Mesa, MD: ET represents roughly 150,000 patients in the US with a median age of presentation in the early 60s. These can range from being young—there are teenagers with ET—all the way up to advanced age. Although that’s the median, the distribution is a bit flatter because there are [patients] across each decade. Our goals in ET are particularly around the prevention of thrombosis and bleeding and the improvement of symptoms when we can. There’s been an evidence-driven, stepwise approach to how we treat [patients with] ET. First, low-dose aspirin: I think there’s a fair amount of agreement in our guidelines that JAK2 mutated patients have a slightly higher risk of thrombosis in those settings and might benefit from an aspirin even in lower-risk settings…higher-risk patients being older or having had prior vascular events, perhaps leukocytosis, perhaps difficult symptoms. Patients who require cytoreduction, which is pretty much everyone other than asymptomatic low risk or those with CALR [calreticulin] who are lower risk, we consider frontline cytoreduction, which currently has been either hydroxyurea or pegylated interferon off-label. It’s not approved for that setting, but we are looking at trials potentially in the long-acting interferons. Ruxolitinib can be considered for those with splenomegaly, again off-label, but it can be really helpful. Anagrelide can also be helpful, and it’s approved in the setting for ET. It does however have a bit more [adverse] effects, [gastrointestinal], palpitations, others, so it tends to be something we keep in the bag.

Naveen Pemmaraju, MD: This is excellent. John, in the second field, polycythemia vera [PV] has seen some unexpected progress in the past few years, and again highlighted at ASH. John, if you could talk about some of the developments in PV, in the novel interferons, the hepcidin mimetics. Take us through PV in 2022.

John Mascarenhas, MD: PV is a myeloproliferative neoplasm. Much like Ruben said, characteristics are like essential thrombocythemia, and the goals, for the most part, are the same. It’s to reduce the risk of thrombosis, and to that effect, we have several agents that we’ve been using for years, hydroxyurea, anagrelide, and interferons. More recently and excitingly, we had a new approval in November 2021 of ropeginterferon for patients with PV, and that provides another FDA-approved option for our patients with polycythemia vera. More recently, there are data coming out from a phase 2 study of a hepcidin mimetic, rusfertide, which is a different concept than interferon. Interferon is a biologic, it’s an anticlonal, anti–stem cell directed therapy. It can control the counts, but perhaps more excitingly, it has the ability to reduce the driving mutation level, and that is thought to associate and correlate with outcome measures that matter, that we strive for, [such as] progression-free survival and overall survival; things that we can’t easily measure in a clinical trial. Rusfertide is a little different. It’s a drug that affects hepcidin mimetic, and iron metabolism and distribution, and essentially limits iron’s availability for erythropoiesis in the bone marrow. By doing that, you control the hematocrit and remove the need for phlebotomy. Unlike interferon, it’s not a stem cell–directed therapy, but it is an effective therapy in phase 2 setting for removing the need for phlebotomies in those patients where that might be an unmet need, a significant phlebotomy requirement.

Transcript edited for clarity.

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