Ruxolitinib Therapy for Patients With Myelofibrosis

Ruben A. Mesa, MD, FACP:The consistency of the real-world experience with ruxolitinib compared with the clinical trials is very significant. As one of the investigators on that study, it’s very gratifying. I continue to utilize ruxolitinib very actively in my practice, as well as see many patients who have been treated with it. Indeed, it has become the standard, and it’s become the standard because the experience that both treating physicians and patients have found is very consistent. It’s beneficial. It has a real impact, and the improvement in symptoms and spleen in patients with myelofibrosis is not cosmetic. Those are surrogate markers of response that lead to, first, a real clinical benefit to the patient, but I do think they truly impact the biology of the disease in a way that’s favorable for patients. They live longer, they are more active, they have fewer complications, and the degree of stability they experience is of sufficient length to really highlight the significant impact that is being seen.

The safety profile of ruxolitinib has become well described over the intervening years. Cytopenias are certainly the most common toxicity that can be seen. Indeed, they are almost an on-target effect in that the inhibition of JAK2 impairs erythropoiesis and the creation of platelets. So certainly, dose modification is to be expected.

Other toxicities are relatively uncommon. They may include headache and a range of things. Longer term, we have seen that there is a slightly higher risk of certain atypical infections if a patient has known hepatitis B or tuberculosis. Fortunately, these are not common things in the United States, but they are in other parts of the world and, they can worsen those atypical infections. There can be an increase in herpes zoster infections, or reactivation of herpes zoster, or shingles. That is something that we are mindful of.

There have been other things that have been identified, such as a higher rate of nonmelanoma malignancies, or cutaneous malignancies. It is difficult to separate out both the increased baseline risk in patients with MPN [myeloproliferative neoplasms], which has been clearly described, as well as a contributory effect of hydroxyurea, which many of these patients have received in the past.

So we need to be mindful of that as we’re monitoring these patients. I have patients who have a good primary care skin exam or a dermatologic exam at least once a year, or more than once a year if they’ve had prior events.

Transcript edited for clarity.

Case: 72-Year-Old Man Diagnosed With Primary Myelofibrosis

December 2018

• A 72-year old man presents to primary care physician with complaints of fatigue, headache, night sweats, poor appetite, and 10-15lb weight loss over past few months; report of increased abdominal pain over the last 3 months
• PMH: mild hypertension
• PE: BP 130/85; Splenomegaly ~14 cm below left costal margin
• Lab values:
  • HGB: 8.9 g/dL
  • Platelets: 189 x 10⁹/L
  • WBC: 27.2 x 10⁹/L
  • Serum LDH: 1500 U/L
  • Serum EPO: 11.5 mU/mL
• Bone Marrow Biopsy:
  • MF-2
  • Circulating blasts, 1.2%
  • JAK-V617F mutation, del(20q)
• Diagnosis: Primary myelofibrosis