Post-Conference Perspectives: Myeloproliferative Neoplasms - Episode 3
Jamile Shammo, MD, FASCP, FACP, shares insight into the currently available treatment options for polycythemia vera and examines how treatment intolerance and/or resistance can impact the therapeutic approach.
Jamile Shammo, MD, FASCP, FACP: The cytoreductive treatment options include hydroxyurea, which is the most common treatment option for polycythemia vera [PV], and the most commonly utilized dose is 500 mg BID [twice daily]. That’s derived from retrospective data that looked at what the most commonly utilized dose is. That’s not to say that it’s the dose that’s appropriate for every person. Clearly, you want to maintain the dose that’s most appropriate for every patient, aiming to eliminate the requirement for phlebotomy and control symptoms of the disease. That’s why we are utilizing cytoreduction. Obviously, you can increase the dose per the patient tolerability.
When I start cytoreductive therapy, I monitor the patients closely because I have seen patients who have developed mouth sores, mucositis, and GI [gastrointestinal] adverse effects. I’ve noticed that long-term exposure to hydroxyurea is more associated with intolerance and adverse effects. You could see adverse effects in the earlier phase, but that’s less common than cumulative exposure over the course of years. For example, leg ulcers tend to develop after many years of exposure to hydroxyurea.
Relative to the interferons, as I’ve already said, you have younger individuals. I have multiple individuals who are in their 20s, 30s, and 40s. Granted, I have very little data on long-term exposure to hydroxyurea in patients who may be in their 20s, let alone the fact that they would like to have children. Interferons tend to be the other drug that I fall on for this, but you have to be very cognizant of the psychiatric adverse effects like depression as well as liver function abnormalities and the cytopenias that will come with that as well, of course.
Going back to Hydrea [hydroxyurea] resistance and intolerance, there are ELN [European LeukemiaNet] criteria that have been described to help physicians understand the exact definition of what Hydrea [hydroxyurea] resistance and intolerance may be. Resistance essentially means that your patient has been on at least 2 g of hydroxyurea for a minimum of 3 months and continues to require phlebotomy, continues to have uncontrolled hematocrit, and has a higher white blood cell count. There’s no control of the spleen or spleen-related symptoms, and those patients are not responding appropriately; they’re resistant to the drug that you are utilizing.
Intolerance references the inability to tolerate the drug by the manifestation of hematological toxicity with a low neutrophil count below 1000 or low hemoglobin, developing cytopenias that could preclude delivery of this drug. It may also be manifestations of nonhematologic toxicities like what we’ve talked about with mucositis, GI adverse effects, pneumonitis, which I’ve seen very rarely. It could also be leg ulcers, which can be a problem because they would not heal unless you stop the offending drug. People sometimes do not make the connection between leg ulcers in older individuals and exposure to hydroxyurea because physicians and patients may think that it is related to things like peripheral vascular disease, poor circulation, etc. It’s important to remember that prolonged exposure could be associated with that and, without stopping the drug, you will not be able to tackle this particular difficult-to-treat problem.
TRANSCRIPT EDITED FOR CLARITY