Evaluating Cytoreductive Approaches in MPNs

Douglas Tremblay, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, discusses the different cytoreduction approaches available to patients with myeloproliferative neoplasms (MPNs), specifically essential thrombocytopenia (ET) and polycythemia vera (PV), and the safety profiles of these agents.

Transcription:

0:09 | The different set of cytoreductive approaches available for patients depends on which disease you have. If you have ET, the frontline therapies include hydroxyurea or pegylated interferon. If you have polycythemia vera, it is hydroxyurea, pegylated interferon, or ropeginterferon alfa-2b [Besremi] given at a once every 2-week dose. These options are available in the frontline.

0:33 | In second-line settings, there are additional options available such as the JAK 1/2 inhibitor ruxolitinib in polycythemia vera, as well as the selective platelet reducer anagrelide in patients with essential thrombocythemia.

0:47 | In terms of safety profile, I'll focus first on hydroxyurea and interferon-based therapy. Hydroxyurea is an oral pill that is frequently taken once a day. [Adverse] effects of this include hematologic toxicity [in] other cell lines, including reducing white blood cell count, as well as reducing platelet count or hemoglobin, which is desirable in some patients, but also can introduce toxicities where you could try to control the blood count that is abnormally elevated in and PV or ET. [Adverse] effects of hydroxyurea outside of hematologic toxicities include some mouth ulcers, particularly in higher doses, or skin ulcers, particularly around the medial malleolus that can lead to discontinuation of the drug. There is also an increased risk of non-melanoma skin cancer that is induced with hydroxyurea.

1:38 | In terms of pegylated interferon, it is an injectable medication and a frequent [adverse] effect is a flu-like syndrome that happens after the first dose. It usually gets better over time. Concerning [adverse] effects that informed selection of this agent vs other agents include its neuropsychiatric [adverse] effects in patients who have severe depression or anxiety or psychiatric disorders. It is largely contraindicated in those diseases, as well as exacerbating autoimmune diseases. There is also hepatotoxicity and ocular toxicity which require monitoring as well. Importantly, in younger patients, particularly those who are trying to conceive or trying to get pregnant, pegylated interferon is safe in that setting and hydroxyurea cannot be used.