Expert Reviews the Current State of the Essential Thrombocythemia Treatment Paradigm

September 14, 2020

In an interview with Targeted Oncology, Prithviraj Bose, MD, discussed the disease outcomes for patients with essential thrombocythemia, as well as the unmet needs and therapeutic strategies available in this space.

The survival outcomes for patients with essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), are generally no different than the survival of an age- and sex-matched healthy person, meaning this is a rare disease type in which oncologists are able to tell patients that their diagnosis will not reduce their life expectancy. The mainstay of treatment has been hydroxyurea.

Although ET does not come across as a disease with many unmet needs due to the survival expectations, some challenges still must be overcome. For example, the current therapeutic options do not help with symptoms. The JAK inhibitor ruxolitinib (Jakafi) is currently in development for the treatment of patients with ET, which may be helpful in managing symptoms. Ropeginterferon alfa-2b (P1101) also appears promising in this setting, considering its approval in Europe for the treatment of polycythemia vera (PV) and the FDA’s recent acceptance of a Biologics License Application for this agent as treatment of patients with PV in the absence of splenomegaly.

The National Comprehensive Cancer Network (NCCN) Guidelines recommend the use of the International Prognostic Score of Thrombosis (IPSET=thrombosis) to assess the risk of patients with ET. Stratifying patients by IPSET risk is important to managing patients and treating them accordingly.

In an interview with Targeted Oncology, Prithviraj Bose, MD, associate professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discussed the disease outcomes for patients with ET, as well as the unmet needs and therapeutic strategies available in this space.

TARGETED ONCOLOGY: What does the prognosis generally look like for these patients with ET?

Bose: For patients with ET, fortunately, we are able to tell them, and this is rare for an oncologist to be able to do, but we were able to tell them that for the most part, their survival is no different from an age- and sex-matched healthy person. ET, if you consider all comers, does not reduce your life expectancy, but there will be some patients who will progress to myelofibrosis. There are fewer that will transform to AML, which is an devastating diagnosis, but ET, overall across the board, has a normal life expectancy.

TARGETED ONCOLOGY: What are the current treatment options that you discussed in your presentation?

Bose: We start with what we all use; the bread and butter treatment is hydroxyurea for high-risk patients and maybe even intermediate-risk patients. The data are supporting that and over and over. Interferons are used in certain centers, although not so much at ours, but those are another very reasonable option. Those are your standard therapies. Ruxolitinib is in development, but the JAK inhibitor is not approved yet.

TARGETED ONCOLOGY: What are some of the new and emerging treatment options that you'd like to discuss?

Bose: It’s always exciting to be talking about new mechanisms of action and new things on the horizon. Unfortunately, there are not that many in ET. Now the issue in ET is that because survive is so good, the drug development in ET is not as much of an unmet need, so to speak, as in some of the other cancers which have a much worse prognosis. I think that is an important thing to keep in mind.

Now, there are some unmet needs. For example, symptoms are not well addressed by any of the current therapies. That’s why I think ruxolitinib would make a very important difference. Also, there is now interest in this new interferon, it's called ropeginterferon alfa-2b. It has the trade name of Besremi in Europe, where it got approved in the beginning of 2019 for PV. There is interest in that for in ET, and there is a trial that has been publicly announced, so we'll see how that goes. However, that might be a really novel treatment for ET because we know that interferons can give you deep molecular responses, and this is a long-acting one, so you'll give it every 2 weeks initially and then every 4 weeks, so this could be something really nice for patients with EGFR.

TARGETED ONCOLOGY: What are the NCCN guidelines for ET right now?

Bose: The NCCN guidelines for ET do embrace what we call the revised IPSET thrombosis model. If that is your international prognostic scoring system for ET, there's just an acronym for that, so the revised IPSET thrombosis model divides patients into very low, low, intermediate, and high rates. That's what the NCCN actually supports using, and that's what I use in my own practice, for example, as well.

Basically, for the very low-risk patients, you can just watch them. For the low-risk patients, you should be on aspirin. In the intermediate-risk patients, it really comes down to preference, but you could argue that they can do with just aspirin, although it would be more conventional to give them cytoreductive therapy. I think most people would [receive cytoreductive therapy], and high-risk patients absolutely need cytoreductive therapy in addition to aspirin.

TARGETED ONCOLOGY: What do you hope that the audience took away from your presentation?

Bose: ET is not a disease in which I have a lot to say about new drugs, so I think the points that I would hope the audience focuses on are the revised IPSET model and how we risk stratify patients and manage them accordingly, as well as the data with interferons, which may be as good as hydroxyurea, although interferons have some downsides, and then things like the distinction from prefibrotic primary myelofibrosis are very, very important. I would say that with some of the newer drugs, which are interesting mechanisms and the data with ruxolitinib, those will be some of the things that I would mention as takeaways.

TARGETED ONCOLOGY: What advice would you like to share with a community oncologist who comes across a patient with ET in their practice?

Bose: The first thing that comes to mind is that we do not focus on the platelet count, as much as traditionally we might have. That's very, very important, so it's a little counterintuitive. I understand why it's difficult; the hallmark is high platelets, and high platelets must be bad. The goal must be to normalize them. That’s been sort of the traditional dogma, but no study has shown that the platelet count correlates with clotting risk. It's really not that important to control the platelets unless the platelets are above a million and a half. In that situation patients bleed, not clot, so that's a different problem. I hope that community oncologists take away ifrom this that platelet count per se is not a thrombotic risk, whereas the thrombotic risks are age, JAK2 mutation over other mutations, prior thrombosis, and maybe leukocytosis.