Symptom burden lifted for rare blood cancer

“I’m alive today because of a clinical trial,” he says of a Phase I study he entered at MD Anderson four years ago for his myelofibrosis, a rare blood cancer that had no standard treatment at the time.

Last year, he and wife Sandy celebrated their 45th wedding anniversary. They live in Kingwood, north of Houston, near their son’s family, and enjoy strong connections to their two grandchildren.

The 68-year-old retiree is not exactly retired. He puts the communications skills honed during a career in agricultural public relations in the Midwest to good use as a volunteer for two chambers of commerce.

Harris is also self-employed as an insurance agent specializing in long-term care insurance, annuities and life insurance.

First sign of hope

The drug Harris received on that earliest-stage study — and has taken ever since — went on to become in November 2011 the first drug ever approved by the U.S. Food and Drug Administration to treat myelofibrosis.

Srdan Verstovsek, M.D., Ph.D., associate professor in MD Anderson’s Department of Leukemia, led that Phase I study and was principal investigator on every U.S. clinical trial for ruxolitinib, developed by Incyte Corporation. It is known commercially as Jakafi^™.

Myelofibrosis strikes about 3,000 Americans annually. A build-up of malignant cells in the bone marrow triggers inflammation that scars the bone marrow, eventually causing severe anemia, swelling of the spleen and liver, extreme weight loss and, ultimately, death. The debilitating symptoms contribute to a poor quality of life.

“We previously had no therapies to attack the molecular abnormalities that cause myelofibrosis. The emergence of ruxolitinib has been a major improvement for our patients. They feel better and live longer,” Verstovsek says.

“The clinical trials showed ruxolitinib provided very good control of the symptoms of myelofibrosis, including spleen shrinkage, liver reduction, and improvements in the patients’ ability to walk, eat and gain weight. A Phase III trial showed a survival benefit, too.”

With no approved therapies, oncologists tried chemotherapies approved for other malignancies combined with supportive care, mainly blood transfusions. About 10% of patients are eligible for bone marrow transplants.

When these off-label drugs work at all, the effect usually lasts only 6 to 12 months, Verstovsek says.

Heavy symptom burden

In Harris’ case, a variety of drugs kept the disease at bay for two years before his oncologist referred him to Verstovsek. “My doctor had heard Dr. Verstovsek speak about this new drug at a meeting.”

Myelofibrosis comes with a formidable set of symptoms, including:

• Abdominal pain
• Exhaustion
• Steep weight loss
• Night sweats
• A powerful and persistent itching sensation
• Bone pain
• Expansion of the spleen to the extent that it suppresses appetite, affects breathing and makes it difficult to bend or walk

End-stage patients resemble those dying of starvation, with huge abdomens and emaciated limbs.

Harris had the swollen spleen and vividly recalls being too tired to leave the house. “I couldn’t walk up a single flight of stairs without resting.”

Some patients, Verstovsek notes, have lost 30 to 50 pounds as their disease progressed. Many regain it all and more when taking the drug. “The main long-term side effect of this drug appears to be weight gain,” he says.

He estimates 80% of myelofibrosis patients receive some clinical benefit from ruxolitinib.

Not a cure, but considerable relief

Even with major symptom relief and extended survival, ruxolitinib does not cure the disease or reverse damage to bone marrow.

“It doesn’t get any worse or any better,” Verstovsek says. Eventually, the drug stops working, but responses tend to be durable and many patients have been on ruxolitinib for four or five years.

Verstovsek’s practice focuses on myeloproliferative neoplasms, which also include polycythemia vera, overproduction of red blood cells, and essential thrombocythemia, overproduction of platelets.

He sees 200-250 new patients annually and also heads MD Anderson’s Clinical Research Center for Myeloproliferative Neoplasms, a new center formed last year in the Department of Leukemia and funded by philanthropy.

It’s a far cry from the situation when Verstovsek joined the faculty in 2001. Then, about 60 patients with any myeloproliferative neoplasm came to MD Anderson annually.

When the JAK2 mutation was discovered in 2005, opening the door to a possible treatment, Verstovsek sprang into action. He identified potential patients through advocacy groups, online chat rooms and other channels and reached out to drug companies to bring them together for clinical trials to finally address the disease.

MD Anderson typically has 10 or more open clinical trials for drugs from a variety of companies to treat myeloproliferative neoplasms.

This is comforting for Mike Harris. “Dr. Verstovsek tells me if this stops working, he’s got four more drugs in the pipeline.”