Treatment Considerations in Myelofibrosis

Ruben A. Mesa, MD, FACP:When determining treatment for patients with myelofibrosis, I am mindful of 2 things: First, the patient’s prognosis. Are they low, intermediate, or at higher risk, depending upon whatever score you choose to use. The majority of patients are intermediate to high risk. The minority presenting with a lower-risk profile, particularly if we are quite studious in terms of trying to find those risk factors—it’s only a minority, perhaps 20% or less who really are low risk. So the majority are intermediate or high risk.

Secondly, I look to see what the burden of disease that they’re facing is. Is there anemia? Are there symptoms? Is there enlargement of the spleen? Is there movement toward acute leukemia, or is there progression? I say this because the 2 issues are complementary. The decision-making first begins with: Should a patient proceed toward a stem cell transplant in the near future or not? I believe that is a consideration according to our current guidelines for patients with intermediate- and high-risk disease, particularly if they’re younger.

There are many variables that factor into that decision for having a stem cell transplant. Is there a donor? What is the exact prognostic risk for the patient? What is the patient’s age? What is the patient’s desire toward going to a stem cell transplant? It is one of the most complex medical therapies we have. It carries with it significant risk. Anyone who says that is an easy decision for a patient is clearly not the individual facing the decision. It’s a very complex part.

So first I make that decision with the patient. Transplant in the near future? Transplant in the distant future? Or, likely, no transplant at all? Then we evolve into the discussion of medical therapy. Medical therapy has the potential to benefit the majority of patients with myelofibrosis. According to our current NCCN [National Comprehensive Cancer Network] guidelines, for asymptomatic, low-risk patients we may choose to observe them or place them on a clinical trial. But for individuals who are low risk and symptomatic, intermediate-1 or higher risk, we will at least consider medical therapy, potentially with ruxolitinib.

The patient we are discussing is 72 years of age and has intermediate-2 risk disease. So the question arises: Should we consider a stem cell transplant for this patient?

It would be a discussion. It would be accurate to say that the minority of 72-year-old patients who would like to proceed with a stem cell transplant have an appropriate donor and are felt to, overall, be good candidates for stem cell transplantation. In the majority of such individuals, we likely would go with medical therapy. But as with all things, there are exceptions, depending upon the physiologic health of the patient, how aggressive they really wish to be in terms of their healthcare, and clearly, the resources available to them.

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