Polycythemia Vera: Optimizing Ruxolitinib's Role

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Ruben Mesa, MD:The standard starting dose for ruxolitinib in patients with polycythemia vera is 10 mg twice a day. And I think for most individuals, that is a very logical place to begin. There are times patients do benefit from dose increases. Over time, what I would monitor in this individual is 1, is the splenomegaly resolving? Two, are the counts being controlled? Do they need less phlebotomies, do they become phlebotomy independent? Three, are the symptoms improving? Clearly, at the same time, we’re monitoring for improvement in the leg ulcer. As I mentioned, that can be a lengthy healing process, so I don’t think that occurs immediately, but that certainly takes time. So, we’re monitoring all of those aspects. Now, if we were to find after a period of time, at least 8 weeks or more, that we still have residual splenomegaly, or difficult symptoms, or the counts are still a little higher than we would like, I really do not hesitate to increase the dose.

Patients with polycythemia vera can be up to 25 mg twice a day of ruxolitinib. Things that can be drivers of needing higher doses are individuals with very high counts. So, that individual might need a higher dose. Another driver is very severe or extreme symptoms, very difficult or refractory pruritus—has not been a major driver in this individual but it’s not uncommon for these individuals sometimes to benefit a bit more than the 10 mg twice a day. But individuals sometimes are quite sensitive so starting at 10 twice a day is not unreasonable.

As I follow patients long-term with ruxolitinib, I am reassured by our 4-year data from the RESPONSE study recently presented at the 2017 American Society of Hematology meeting. After 4 years, we were able to identify that ruxolitinib does not seem to have any unexpected long-term negative consequences of use. There are modest side effects that we can track. We know after 4 years, there seems to be some rate of herpes shingles that individuals can develop that was identified early on. That’s less than 10%, but that is 1 risk that we monitor for. Another is we know that we’re monitoring these patients for increased risk of nonmelanoma skin cancers.

Now I think this is multifactorial. Individuals with MPN tend to have a much higher rate than the general population of non-melanoma skin cancers. We know they all run hydroxyurea kind of by definition of trial entry. That is a factor. Whether ruxolitinib contributes to a risk of non-melanoma skin cancers, it’s good to differentiate, but at least we’re mindful of it. It is in the FDA label, so it’s something just to be mindful of watching. But in general, it’s a pretty well tolerated drug. Through 4 years of therapy, we see durable responses of control of the hematocrit, improvements in splenomegaly, phlebotomy independence, improvement in symptoms, and likely a decrease in the rate of thrombosis.

As I mentioned, I start patients on 10 mg twice a day. I may increase it if I see there are opportunities and better control of the spleen symptoms or counts. I may decrease it if I see that the blood counts drop to an excessive degree. Dose decreases are probably more common in utilizing ruxolitinib in therapy with myelofibrosis where cytopenias might be more prevalent. In polycythemia vera, I find it is relatively infrequent that I need to be lowering the dose. I monitor patients with blood counts as well as periodic physical exams and discussions around their symptoms. The frequency of the blood counts depends a bit on the quality of the response, how stable their blood counts are, and whether they truly have become phlebotomy independent, or we need to have enough blood count monitoring being done to be sure to capture when a phlebotomy is indicated.

Transcript edited for clarity.


June 2016

  • A 49-year old male presents with headache, fatigue, and pain under his left ribs
  • PMH includes depression and newly diagnosed hypertension
  • Physical Exam: BP, 160/90; Abdominal exam reveals splenomegaly — spleen palpable 6 cm below costal margin
  • Laboratory values:
    • Hb=20.7 g/L
    • HCT= 59.4%
    • WBC=10.2x109/L
    • Platelets= 325 x109/L
  • Bone marrow biopsy:
    • MF-1 fibrosis and megakaryocytic hyperplasia with atypia
    • JAK2-positive
  • Patient was started on phlebotomy as needed and aspirin 81 mg

October 2016

  • Patient returns 4 months later with continued headache and dizziness
  • He has had 3 phlebotomies in the past 3 months
  • Patient was started on hydroxyurea 1000 mg/day

January 2017

  • Patient returns 3 months later with abdominal fullness, continued fatigue, difficulty concentrating, fever, and leg ulcer
  • Laboratory values:
    • Hb= 22.4 g/L
    • HCT= 65.3%
    • WBC=13.3x109/L
    • Platelets=153x109/L
  • Patient is started on ruxolitinib
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