Managing Patients with Essential Thrombocythemia


Dr Ruben Mesa describes how he treats patients with essential thrombocythemia and the available treatment options.

Rami Komrokji, MD: Ruben, how do you think about treating those patients? What are the treatment options? How do you manage ET [essential thrombocythemia]?

Ruben Mesa, MD: First, it’s key to understand the prognosis and the burden the patient faces. There’s a prognosis and the risk of vascular events, which we’re trying to prevent. Additionally, we have to be mindful of how they feel. I look at both factors. Following our NCCN [National Comprehensive Cancer Network] Guidelines that many of us participated in developing, first we recognize that most patients probably benefit from a baby aspirin. There’s some controversy. Is that overkill for individuals who are calreticulin mutated? Their risk is a little lower. But for most, I consider a baby aspirin. There are some data showing that a baby aspirin twice a day in patients who are still a little symptomatic [is beneficial].

For medical therapy, we have 2 options for frontline therapy in the NCCN guidelines. [The first option is] hydroxyurea [Hydrea], a pill that’s usually fairly well tolerated overall. It isn’t disease modifying, but it controls the blood cell counts and decreases the risk of vascular events and some adverse effects, including GI [gastrointestinal]. Cutaneous had a higher risk of nonmelanoma skin cancers and mucocutaneous ulcers. Not everyone tolerates hydroxyurea. Not everyone is able to take enough hydroxyurea to control their blood cell counts.

The second option is interferons and long-acting interferons. In the United States, there has historically been pegylated interferon at low dose, 45 mcg a week, or 90 mcg a week—something in that range—to get the platelets under 400,000 per mm3 and control the blood cell counts. There’s a phase 3 study that [Srdan] Verstovsek [, MD, PhD,] and I are leading called Surpass-ET [NCT04285086]. This is with a new formulation of interferon called the ropeginterferon alpha-2b that was approved in November of 2021 for polycythemia vera [PV]. But in ET, that’s being looked at as an option compared with anagrelide in the second-line setting for individuals with ET. This may potentially replace pegylated interferon in those recommendations. It isn’t in the guidelines, but that may change.

We feel that the advantages of interferons over hydroxyurea may have a deeper impact on the stem cell clone. It may potentially help decrease the risk of movement toward myelofibrosis longer term. It’s probably safer to use during pregnancy or gestation, which are all positive things. A lot of individuals can be younger. The downsides include that it’s a bit more complex to take. It’s a subcutaneous injection. It can have adverse effects in terms of flu-like symptoms, and it can rarely increase the risk of depression, but not insignificant. It rarely has caused autoimmune disease.

Those are the therapies we use the majority of the time. Anagrelide remains. Anagrelide is very helpful for lowering platelets. I find that patients usually do better with anagrelide as combination therapy than monotherapy for people with platelet counts that are more difficult to control. There remains a role for JAK inhibition, ruxolitinib, for individuals with splenomegaly symptoms.

Other things are in the guidelines. It typically is second- or third-line therapy, but helpful. Some new therapies are coming down the pike, including LSD1 inhibition, which has been active in that setting. We’ve had a trial with that. There are more things coming. Longer term, there will maybe even be targeted approaches toward calreticulin. We’re seeing a growing list of options for ET.

Rami Komrokji, MD: Absolutely. On the trial for the ropeginterferon, the control arm is the anagrelide, right?

Ruben Mesa, MD: Correct. In symptomatic individuals, they have some degree of leukocytosis and have failed hydroxyurea. If you have patients who fit that description, consider referring them for the trial. It will be a benefit for patients with ET to successfully demonstrate the benefit of interferon. We’ve seen it in other settings. We did an MPNRC [Myeloproliferative Neoplasms Research Consortium] clinical trial with pegylated interferon alpha-2a that all of you participated in where we clearly saw benefit in the front line and second line. Pegylated interferon alpha-2a is a good drug, but at this point, no one has tried to advance it for registration. It still remains in a bit of an uncertain state in terms of production and from a regulatory standpoint.

Jamile Shammo, MD, FACP, FASCP: It’s certainly an area of need because it’s difficult to treat patients who are Hydrea resistant or intolerant with ET. Hopefully it’ll be a positive trial.

Ruben Mesa, MD: I see a lot of patients who are managed on their maximum tolerated dose of hydroxyurea even if it’s inefficient and ineffective. This will be relevant as we switch to PV. When patients are on 500 mg of hydroxyurea a day but their counts are still high and they’re still symptomatic, we aren’t accomplishing anything. But the doctors feel, “I can’t raise the hydroxyurea any further because they aren’t tolerating it.” We definitely need other options.

Rami Komrokji, MD: Absolutely. It’s an underutilized option in the community. Maybe community oncologists don’t think of interferon or there’s fear about using the drug. For me, it’s also the appeal that this could alter the natural history, because we sometimes underestimate the risk of ET or certain selected patients whose survival is impacted by this disease.

Transcript edited for clarity.

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