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For many patients with polycythemia vera, hydroxyurea is a beneficial first-line treatment. But that’s not the case for everyone. One expert discusses which drugs should be used next.
While hydroxyurea is a tried-and-true frontline therapy for patients with polycythemia vera (PV) — a type of myeloproliferative neoplasm (MPN) – some patients do not respond to this treatment.
OncLive, a sister publication of CURE, sat down with Abdulraheem Yacoub, M.D., associate professor of medicine at the University of Kansas Medical Center, about what the best treatments are for patients who do not do well on hydroxyurea, as well as some exciting advances in research in this field.
Can you give an overview of managing patients with PV after they fail on hydroxyurea therapy?
Hydroxyurea has been our first line therapy for PV for decades. It's a very effective therapy when it works. It's still very successful in the majority of patients who receive it. But there is a fraction of the patient population that still do not do well with hydroxyurea, and they experience either early or late failure.
It's an unmet need. Those patients have poor outcomes and they have significant morbidity, and it's great to live in a world where we can offer them better options. So, we discussed some of the approved and upcoming options and future research that can help move this forward.
What agents do we currently have for these patients?
One of the options that we have already is Jakafi (ruxolitinib), which is a JAK1/JAK2 inhibitor. The use of Jakafi in PV makes perfect sense, given that this is a JAK2-driven malignancy. Therapy with Jakafi has proven to be effective in multiple randomized, phase 3 clinical trials. The response rate in the control is about 60 percent in both studies. In addition to this, Jakafi was associated with other benefits, such as spleen reduction, spleen symptom improvement, improvement in the general symptoms of the patients and quality of life, as well as more favorable iron metabolism to avoid iron deficiency.
Is there an advantage of Jakafi over interferon?
So Jakafi, being an oral agent, is defiantly more convenient. It does result in a very rapid response and a very effective response. As far as we know, it's a durable response. It is not disease-modifying in the sense that it does not necessarily prevent disease progression or transformation that we can prove at this time.
Interferons are a class of drugs that are synthetic equivalents of a naturally produced hormone that can result in direct toxicity to the cancer and also can harvest the immune system to try to achieve immune-mediated responses in those patients. We have not yet proven that this actually does change the paradigm or change the natural course of these cancers. But the body of evidence is very convincing that these drugs are very active with some deep responses and some complete molecular responses, which is very intriguing and definitely worth further follow-up. The long-acting interferons are being used in the hands of experts, and the toxicities are associated with it can be controlled to allow patients to receive the benefit of the therapy.
How do you choose treatment for these patients?
So far, hydroxyurea. remains our first monotherapy. However, interferons are also making themselves as a very legitimate first-line option, especially in young patients who are going to live with the therapy for longer, and they might wish to avoid some long-term side effects of hydroxyurea. It also is important for younger patients who wish to preserve fertility and to have a chance at achieving a deep molecular response and looking at potentially an effective therapy where they can be on a low-dose maintenance or off-therapy for a while.
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