Selecting Second-Line Therapy After Hydroxyurea in Essential Thrombocythemia
John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai, New York, New York, reviews a case of essential thrombocythemia in which hydroxyurea failed to provide adequate blood count control at the maximum tolerated dose. He discusses the overlapping resistance and intolerance that prompted a change in therapy and the rationale for selecting ropeginterferon alfa-2b. He also highlights treatment goals, potential disease modification, and practical monitoring considerations.
Transcript:
Hi, I'm John Mascarenhas from the Icahn School of Medicine at Mount Sinai in New York City. And today we're going to be reviewing, I would say, a classic case of hydroxyurea resistance and intolerance in a patient with essential thrombocythemia.
This older woman was having trouble balancing the toxicities of hydroxyurea at higher doses, closer to 1000 mg per day, getting more of the mucositis, which is common, and then also hematologic toxicity, treatment emergent-leukopenia, and anemia. And then at lower doses, the thrombocytosis was predominant associated with headaches.
This patient was clearly not able to achieve a hematologic response and tolerability with hydroxyurea. This is exactly the kind of patient one should be thinking about second-line options, NET based on the SURPASS ET study, ropeginterferon alfa-2b is a great option for a patient like this.
And this is the kind of patient where we're looking to achieve the primary end point of the SURPASS ET study, which is count control, so a white count less than 10,000, a platelet count less than 400,000 and the absence of progressive symptoms, splenomegaly, or a thrombohemorrhagic event. So thrombotic risk reduction is the reason why we intervene and we prescribe medications like ropeginterferon alfa-2b.
But I would also argue that it's not just thrombotic risk reduction, which is of course why we intervene, but also the potential to disease modify over time. And the surrogate for that of course is reduction in JAK2 V617F or mutant CALR variant allele fraction, which has been shown now in multiple studies, including the SURPASS ET study, even with longer follow-up, to be more obvious with interferon, which is a stem cell or anti-clonal directed therapy compared to anagrelide or hydroxyurea.
In this patient, I think there's two potential benefits, better count control with the potential for less toxicity and then potential disease modification over time. For those of you that saw that she had depression that was well controlled on antidepressants, that would not be a strong stop or contraindication for using interferon, but one should be aware of the potential for neuropsychiatric toxicity and one should be prepared for a slower response with interferon sometimes. And the dosing of course here is 250, two weeks later, 350, and then by four weeks, 500 micrograms at a flat dose every two weeks administered by the patient at home.
Follow the CBC, the chemistry, the thyroid stimulating hormone, as well as yearly ophthalmologic exam and lipid profile. Otherwise, this would be an ideal patient for interferon alpha 2B. And this represents, I would say, a rather sizable majority of patients who are receiving hydroxyurea.
