Ruxolitinib for Treatment of Polycythemia Vera


Harry P. Erba, MD, PhD: We do know that this is a JAK2-driven disease. What is the relevance of JAK2 to controlling disease when other cytoreductive therapies have failed, Ruben?

Ruben A. Mesa, MD, FACP: I think the JAK inhibition as a strategy in PV [polycythemia vera] is very logical, based on what we know with the disease. Even in the initial studies that focus on JAK inhibition in myelofibrosis, the reason that it didn’t really start in PV was that the agents hadn’t been tested first in human studies, so start on the patients with the most advanced disease. P vera [polycythemia vera] was almost the most natural place for the utilization of JAK inhibition. The vast majority of patients with PV have a JAK2 V617F mutation. They all have overactivation of the JAK/STAT pathway. Certainly, that blockade of the JAK/STAT pathway has an impact, not only in terms of controlling the counts in a favorable way and control of erythrocytosis and thrombocytosis that are both JAK2-dependent, but also a very significant improvement in the cytokines associated with the disease, improvement in symptoms, and reduction in splenomegaly, as had been seen by the earlier myelofibrosis studies.

Now, ruxolitinib has been approved as a JAK inhibitor in P vera patients who have been resistant or intolerant to hydroxyurea or earlier cytoreductive therapy, whatever that is, and in particular, helpful for improvement of controlling counts when they had failed prior therapy and improvement in those difficult symptoms, including reduction in splenomegaly. It’s been highly impactful.

Harry P. Erba, MD, PhD: Mary Frances, help us with how you actually manage patients with PV on ruxolitinib.

Mary Frances McMullin, MD, FRCP, FRCPath: Ruxolitinib is licensed second-line in patients who are hydroxycarbamide-resistant or intolerant. It’s a group of patients who had a failed response to that. The licensed dose in polycythemia vera is 10 mg twice a day, and that’s usually the dose you start with. The dose adjustments are not usually needed. Occasionally, they may become anemic, which is a bit of a disaster if this started out needing venesection. Thrombocytopenia is the other one you need to watch for and may have to adjust the dose. It’s usually tolerated pretty well in this group of patients.

Again, you’re using a 10 mg twice a day dose, and they do get some adverse effects. The ones that I’ve been particularly aware of are the infections. The one thing I warn patients about is they may well get herpes zoster, and I’ve seen people getting that a lot. It’s a big problem if somebody has been perfectly OK, and then they get herpes zoster, particularly if they get it repeatedly, which can happen. They also need to be very aware of watching their skin, which they really need to do even on the hydroxycarbamide as well. There is an increased incidence of secondary skin malignancies, which again, may be tied up with the hydroxycarbamide.

Harry P. Erba, MD, PhD: Have you seen a benefit in terms of quality of life by using this?

Mary Frances McMullin, MD, FRCP, FRCPath: Absolutely, yes. This drug is particularly useful for a certain group of patients. The group of patients, in my experience, who do very well are those with a big symptom burden, particularly the ones with terrible itch. Polycythemia vera patients have the aquagenic itch, and some people will tell you they haven’t had a shower for years because they can’t stand water on their skin. Ruxolitinib, in these patients, within days stops their symptoms and has a major impact on their quality of life, including night sweats, etcetera, and will reduce splenomegaly. That’s maybe a slightly different issue as to where they are with their disease. I think there’s a subgroup of people with polycythemia vera for whom ruxolitinib is life-changing in terms of quality of life.

Transcript Edited for Clarity

Related Videos
Aaron Gerds, MD
Justin M. Watts, MD
Mikkael A. Sekeres, MD, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Sylvester Comprehensive Cancer Center
Ashwin Kishtagari, MD
Aaron Gerds, MD
Naseema Gangat, MBBS
Ashwin Kishtagari, MD
Somedeb Ball, MBBS
Rebecca Klisovic, MD
Sunil Iyer, MD