Case 1: A Patient with Disease Progression on Hydroxyurea

Harry Erba, MD, PhD:One of my patients who’s in her 50s was being managed with hydroxyurea and phlebotomy and low-dose aspirin. She continued to need periodic phlebotomies. She was iron deficient, although not symptomatic, that I could tell, from the iron deficiency. But, her major problems were arthralgias, bone pain, and pruritus. After switching her to ruxolitinib for hydroxyurea resistance because of persistent symptoms, her arthralgias, bone pain, pruritus all got better very, very quickly and she was able to go back to a very active life, both volunteering and exercising. With repletion of her iron stores, the fatigue also got better.

The labeled dose of ruxolitinib is 10 mg twice a day in patients with hydroxyurea resistance, or intolerant PV (polycythemia vera). However, there are a number of factors about the patient that should be considered when picking the appropriate dose. Most patients with PV will have maintained platelet counts. However, if a patient is on CYP3A4 inhibitors or inducers, those can affect levels of ruxolitinib. Patients on CYP3A4 inhibitors will cause more toxicity with ruxolitinib, and so you may want to start at a lower dose. In patients with renal or hepatic impairment, you also want to use a dose modification in that situation.

When I’ve used ruxolitinib in patients with PV who have hydroxyurea resistance or intolerance, different features are controlled to different degrees. Symptoms typically get much better. Blood counts and hematocrit control also [gets] better. I’ve had patients have persistent mild thrombocytosis while on ruxolitinib, and so it may not control all of the features of the disease. The spleen, in general, gets smaller during this time as well.

In terms of symptom control, ruxolitinib is effective at reducing symptom burden in these patients. We learned this from the placebo-controlled trial, COMFORT-1 in myelofibrosis. Patients with intermediate- and high-risk myelofibrosis clearly had a benefit in symptom control. And, although the RESPONSE Trial was an open-label study and not placebo-controlled, it’s clear from my own personal experience, that symptoms related to the disease will respond likewise to ruxolitinib.

The remarkable thing about using ruxolitinib, in my experience, is that it’s been very well tolerated. Patients continue to have a normal lifestyle. In fact, they often return to things that they weren’t able to do before. So, unlike some other tyrosine kinase inhibitors that are used in clinical practice, ruxolitinib tends not to cause some of the constitutional symptoms or other symptoms that can impact quality of life. Specifically, if you look at symptoms related to ruxolitinib that occur more than in placebo in the COMFORT-1 Study, it was headache, bruising, and dizziness. But, I believe those were mostly related to patients becoming anemic and thrombocytopenic. And, those symptoms were much less common in the RESPONSE Trial. Other symptoms that patients may have that can affect quality of life include constipation and gassiness. The drug, in general, is very well tolerated without some of the other TKI symptoms that we typically see.

There are definitely certain clinical scenarios where ruxolitinib should not be started. In patients with active infections, especially microbacterial infections or fungal infections, ruxolitinib should not be started until those diseases and infections are under control. In patients who are pregnant, ruxolitinib should not be used. It is contraindicated during pregnancy. Those are the two major contraindications that I would consider for ruxolitinib.

A Patient with Disease Progression on Hydroxyurea

Case 1: