SAN ANTONIO (Sept. 9, 2019) ̶ September is Blood Cancer Awareness Month, and this year patients with myelofibrosis, a rare blood cancer, have reason to celebrate. In mid-August, the U.S. Food and Drug Administration approved the first new medication in nearly a decade for patients with myelofibrosis.
Ruben Mesa, M.D., FACP, was part of the international research team that led development of the new drug. Dr. Mesa is director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center.
And due to the drug’s effectiveness in treating myelofibrosis, fedratinib (brand name Inrebic), is being studied to see if it may also be beneficial for patients with other blood cancers, inflammatory diseases and possibly, one day, for diseases related to aging or that involve blood clots, such as heart attacks or stroke.
Swelling of the spleen a major symptom
On Aug. 16, the FDA approved fedratinib for adults with intermediate-2 or high-risk primary or secondary myelofibrosis. Myelofibrosis is a blood cancer that begins in the bone marrow, where red blood cells, white blood cells and platelets are made. It is one of a related group of blood cancers and chronic leukemias called myeloproliferative neoplasms, or MPNs, that can lead to acute leukemia. Patients with myelofibrosis may experience severe anemia, night sweats, weight loss and significant and painful enlargement of the spleen, an organ involved with filtering the blood.
“Think about a healthy spleen as being about the size of your fist. With myelofibrosis, the spleen can swell to the size of a football or even a full-term pregnancy,” explained Dr. Mesa. He was an investigator on the fedratinib studies while he was a researcher, chair of the Division of Hematology and Medical Oncology, and deputy director of the Mayo Clinic Cancer Center in Scottsdale, Ariz. Dr. Mesa continued his research and advocacy for the approval of fedratinib after being recruited to UT Health San Antonio’s cancer center in August 2017
He has assembled a team of myelofibrosis experts at the Mays Cancer Center who provide care to patients from around the world. And now that the new drug has been approved, the team can now prescribe fedratinib to eligible patients.
“The pressure of the enlarged spleen can be very painful, pressing on nearby organs. Patients also may experience fatigue, night sweats or shortness of breath associated with anemia. Bone pain and weight loss are also common,” Dr. Mesa said. There is no cure for most myelofibrosis patients.
According to the MPN Research Foundation, about 18,000 individuals in the United States have myelofibrosis and approximately 300,000 live with one of the three MPN blood marrow disorders, which also include essential thrombocythemia and polycythemia vera.
Study examines regulation of the JAK 2 gene
FDA approval of fedratinib was based on the Phase 3 JAKARTA clinical trial. The drug inhibits the JAK 2 gene, which makes a protein that promotes the growth and division of blood cells in the bone marrow. The investigators proved that fedratinib regulates part of the chemical process to limit the overproduction of damaged blood cells, controlling the uncomfortable swelling of the spleen and other disabling symptoms.
Before the trial, 289 patients received MRIs or CT scans to measure the size of their spleen. The primary objectives of the trial were reducing the patients’ spleen size by 35% and decreasing overall symptoms by 50%.
Participants were randomly assigned to three groups, with neither the doctors nor patients knowing which treatment was being administered. One group received 500 mg of fedratinib, a second group received 400 mg and the third group received a placebo. The oral medication was taken once a day for 24 weeks.
In the 400 mg group, 37% of patients had spleen reduction of more than 35%, compared to 1% in the placebo group. And while 40 percent of patients in the 500 mg group achieved greater than 35 percent reduction in spleen size, 21 percent had serious side effects, including a small group diagnosed with Wernike’s encephalopathy, a neurological disease caused by a low level of thiamine. For this reason, the FDA recommends the 400 mg dosage and cautions doctors to test patients’ blood levels for low thiamine levels before starting them on fedratinib.
“For these patients, doctors are advised to prescribe thiamine and get this reading up to the recommended level before prescribing fedratinib, and then to closely monitor thiamine levels while the patient is on this medication,” Dr. Mesa said.
Only second drug approved for myelofibrosis
Until fedratinib was approved, ruxolitinib was the only drug available to treat patients with myelofibrosis. “Now with fedratinib, physicians and patients have another treatment option, especially for patients who do not respond well to ruxolitinib,” said Dr. Mesa, who also was involved in the ruxolitinib research.
Dr. Mesa also led development of the National Comprehensive Cancer Network’s Guidelines for Myeloproliferative Neoplasms, published in 2017. In 2018 he was appointed to the national board of directors of the Leukemia & Lymphoma Society.
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UT Health San Antonio MD Anderson Cancer Center is one of only four National Cancer Institute-designated Cancer Centers in Texas. The partnership between UT Health San Antonio and MD Anderson Cancer Center, coming together in the UT Health San Antonio MD Anderson Cancer Center, provides leading-edge cancer care, propels innovative cancer research and educates the next generation of leaders to end cancer in South Texas. To learn more, visit www.UTHealthsaMDAnderson.org.