Addressing Unmet Needs in the Management of Myelofibrosis

Ruben A. Mesa, MD, FACP:There remain a variety of unmet needs in myelofibrosis. Foremost among them, in my mind, is an understanding as to why patients progress. If we truly knew why patients progressed we might have a better surrogate marker. We might be able to track that in a better way. We might be able to design other therapies to really target progression or to complement, perhaps in combination with therapies, ruxolitinib for myelofibrosis.

At the current time, it’s not clear that either our molecular mutation profile or cytogenetics are appropriate prognostic scores. I think it’s probably less regarding prognosis in terms of survival, and better surrogate markers of progression can either be targets or help us adjust or monitor therapy.

There’s a very robust portfolio of clinical trials ongoing in myelofibrosis. I share with patients that this is a time to be very hopeful. They include other JAK inhibitors—including pacritinib, fedratinib—which continue to undergo clinical testing and may become available in clinical trials soon. It includes medications being used in combination with ruxolitinib to try to augment response. There’s ruxolitinib with hypomethylating agents, ruxolitinib with immunomodulatory drugs, and ruxolitinib with novel pathway inhibitors such as PI3-kinase inhibitors.

And then, finally, there are other agents independent of the JAK inhibitor pathway that are being looked at: antifibrotic agents, telomerase inhibition, checkpoint inhibition, the use of long-acting interferons, and others.

At the 2018 meeting of the American Society of Hematology, there were between 20 and 30 trials at various phases of development presented for patients with myelofibrosis. So there is much room to be hopeful.

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