Significance of Ruxolitinib and Unmet Needs in MF

Harry Erba, MD, PhD:What ruxolitinib has done is really drawn some attention to these myeloproliferative neoplasms. And we now have a specific agent for not only myelofibrosis but also a certain class of patients with polycythemia vera. So, I think it behooves us as hematologists to understand the disease process and how it affects patients. Because now we have a real option for them in terms of symptom control, reducing the size of the spleen, and extending survival.

However, there are still great challenges. We know that ruxolitinib can cause cytopenias. It must be remembered that patients who went on these trials were often already anemic, and many were transfusion dependent. That is not an exclusion to giving JAK1/JAK2 inhibitors like ruxolitinib. In fact, in those clinical trials, although the hemoglobin decreased to a nadir about 8 to 12 weeks after starting therapy in myelofibrosis with ruxolitinib, it came back up close to baseline. That might be due to shrinkage of the spleen, control of cytokines, less anemia, or chronic inflammation, but for whatever reason, the anemia did get worse at the beginning but then better later on. So, the important message there is anemia should not stay the hand of a hematologist in treating a patient with this drug. However, it does bring up the difficulty of making sure our patient is aware that they may actually require transfusion after starting this therapy, and at least for some finite period of time.

The other thing is that although ruxolitinib is clearly an advance in terms of the quality of life for our patients, and I believe it’s showing a benefit in terms of survival as well, it’s not a therapy that apparently is targeting the very stem cell here. It has not changed the natural history of the disease.

So, I think we need to really learn a lot more about the pathophysiology and what’s the underlying cause of myelofibrosis in order to better target it with therapies that are coming down the line.

Transcript edited for clarity.

March 2017

• A 67-year old woman presents to her primary care physician with complaints of fatigue, abdominal fullness, night sweats, and 17-lb weight loss over the past 6 months.
• PMH includes hypertension, controlled on enalapril 10 mg
• Abdominal examination reveals spleen palpable 7 cm below the costal margin
• Lab values:
  • HGB: 9.2 gm/dl
  • Platelets: 189 x 10⁹/L
  • WBC: 19 x 10⁹/L
• Bone Marrow Biopsy:
  • MF-3
  • CD34+/CD117+ immunostaining demonstrated 1.2% blasts
  • JAK-V617F mutation
• Diagnosis: Primary myelofibrosis