Why Myelofibrosis Remains Difficult to Treat

A better understanding of genetic drivers is needed to develop more targeted treatments.

Over the past decade, researchers have begun to uncover the complex biology behind myelofibrosis. Nearly 5,000 people in the United States are estimated to be diagnosed with this blood cancer each year.



“We do not yet fully understand the biology behind why myelofibrosis advances in patients,” explained Ruben Mesa, M.D., director of UT Health San Antonio MD Anderson Cancer Center. “Improving our understanding can help us advance treatment beyond the current approved and investigational therapies, which are still being examined to determine how they might slow progression of disease.”

What Is Myelofibrosis?

Myelofibrosis is a rare blood cancer that starts in the stem cells of the bone marrow, leading to the production of faulty blood cells that don’t mature or function properly. Eventually, the disorder results in scarring of the bone marrow, further stifling its ability to produce healthy blood cells.

While some patients may live years without symptoms, others see their disease progress rather quickly. Without enough healthy red blood cells, these patients can develop anemia, leading to fatigue, weakness and shortness of breath. Myelofibrosis can also cause an enlarged spleen and the disorder has a higher incidence in people over age 50.

In addition to monitoring patients closely for any signs of disease progression or other conditions, physicians face the challenge of tailoring treatment. “Myelofibrosis is a variable disease,” Mesa said. “A better understanding of the role of genetic mutations that cause the cancer and refining the prognostic scores could help doctors have a much more detailed assessment of prognosis and determine which treatment options are best for each individual patient.”

Understanding Options

While a stem cell transplant is potentially curative in some cases of myelofibrosis, doctors reserve it for patients fit enough to endure the procedure due to the risk of life-threatening complications. Eligibility depends on several factors, including prognosis, age, overall health and the availability of an appropriate donor.

“The average age of diagnosis for myelofibrosis is about 60 years old, which is toward the latter end of when transplantation is considered safe or effective,” Mesa said. “So it’s not an appropriate therapy for all patients.”

For many patients, the goal of treatment is focused on relieving symptoms, reducing an enlarged spleen and improving blood cell counts. Therapy options for those who are ineligible for a transplant include JAK inhibitors, chemotherapy, immunomodulators and corticosteroids. Not all of these agents target the signs and symptoms associated with myelofibrosis, and researchers are working to find additional options.

There are many reasons to be hopeful in myelofibrosis research – a better understanding of the disease, better understanding of its genetic drivers and better therapies.

Hope for the Future

As with many rare diseases, several unmet needs in myelofibrosis are attracting attention, according to Mesa. “Currently, there are very few targeted therapies approved for myelofibrosis, and we do not have effective therapies for patients with the most advanced forms of the disease.”

There is hope. At December’s American Society of Hematology (ASH) Annual Meeting, researchers presented data from more than 20 clinical trials in myelofibrosis. Treatment options being investigated include JAK inhibitors and combinations that incorporate other agents, like immunomodulatory therapies which adjust the body’s immune responses to disease. Researchers are also exploring treatment strategies that target multiple disease-signaling pathways, which are showing promise in early studies, according to Mesa.

These are positive developments for patients with a disease like myelofibrosis. More targeted therapies may one day allow doctors to tailor a patient’s treatment to their specific symptoms and unique genetic makeup of the disease.

“There are many reasons to be hopeful in myelofibrosis – a better understanding of the disease, better understanding of its genetic drivers and better therapies,” Mesa said.

To learn more about Celgene’s commitment to myelofibrosis and other rare diseases, read “Supporting Research to Find Cures for Rare Diseases.”