Initiating Ruxolitinib for Polycythemia Vera


Jamile M. Shammo, MD:If this patient continues to demonstrate high hematocrit, despite increasing the dose and despite phlebotomy, I would look for other evidence of myeloproliferation; perhaps enlarging spleen, constitutional symptoms. Then, I think you could definitely make a case for initiation of ruxolitinib because the drug has been approved by the FDA and can produce significant improvement in hematological parameters, and reduction in splenomegaly and improvement in symptoms so that there is no doubt that this would be a reasonable candidate provided that it’s not just the hematocrit, but it’s also evidence of myeloproliferation and splenomegaly.

I generally start ruxolitinib at 10 mg/twice a day, which was the starting dose in the clinical trial. And in the clinical trial, they basically allowed for dose escalation or reduction clearly based on hematological toxicity, or the need to control their CBC parameters. About one-third of the patients continued on the 10 mg/twice a day. Most of my patients with PV continue on the 10 mg/twice a day. Most of them don’t have severe thrombocytopenia—as you would see with myelofibrosis where you would have to adjust the dose obviously, but not in this patient population. In fact, in the clinical study, some patients ended up having higher doses than the 10 mg/twice a day, and a proportion had lower than 10 mg depending on their responses.

So, I would start this and then I generally monitor the count every week to 2 weeks to make sure that you’re not obviously dealing with a nadir, that you have to adjust the dose accordingly. I also monitor the kidney and liver function also every 2 weeks. And then, I do this for the first couple of months and later on perhaps reduce the frequency of monitoring. I always alert the patients to the potential of developing anemia because, after all, this is a JAK2 inhibitor, and some degree of anemia and thrombocytopenia is expected. Although, again, as my clinical practice reflects that of the clinical trial, grade 3 and 4 heme toxicity has been very small.

My clinical experience with the agents in the resistant/refractory-to-Hydrea patient population with PV mirrors that of the clinical trial that looked at this agent and compared to this available therapy, that is the RESPONSE trial. So, there’s a reasonable tolerability of the agent. There’s excellent control of the hematological parameters, as well as symptomatology delayed the splenomegaly and constitutional symptoms.

I think it’s very important to risk stratify patients who have PV, and plan a goal of therapy based upon their symptoms, risk stratification, and response to cytoreduction, when those patients start cytoreduction. So, I think it’s important for us to treat PV as a hematological malignancy that needs to be risk stratified and optimized, and we should move forward with choosing alternate agents if the patient is not responding to first-line therapy, despite all intensive efforts.

Transcript edited for clarity.

August 2014

  • A 67-year-old female is diagnosed PV after complaining of fatigue
  • Physical Exam was unremarkable
  • CBC:
    • HCT, 48%
    • WBC, 12,100/μL
    • Platelets, 603,000/μL
  • Mutation testing: JAK2 V617F-positive
  • The patient was started on treatment with low-dose aspirin and hydroxyurea 500 mg/day
  • Her symptoms resolved within 3 months

February 2016

  • She now complains of left upper quadrant pain
  • For 1.5 years, the patient was maintained on treatment; however, for the past 9 months her hematocrit has risen to 48% and she has required 4 phlebotomies in last 6 months
  • Hydroxyurea was increased from 500 mg to 1,000 mg daily
  • Physical Exam: remarkable for splenomegaly

August 2016

  • Physical Exam: still remarkable for splenomegaly, slightly smaller
  • HCT 47.5%
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