In a phase I clinical trial, physicians at The Mount Sinai Medical Center have identified the first drug that appears to stop the progression of myelofibrosis, a life-threatening blood cancer. The investigators found that, at low-doses, panobinostat (LBH589) successfully halted and reversed damage to the blood and bone marrow in several of the forty patients enrolled in the trial. Panobinostat, manufactured by Novartis, is a histone deacetylase inhibitor that affects the chromatin structure of malignant cells.

The study, led by Ronald Hoffman, MD, Albert A. and Vera G. List Professor of Medicine, and Director of the Myeloproliferative Disorders Research Program, and John O. Mascarenhas, MD, Assistant Professor of Medicine (Hematology and Medical Oncology), was published online in the January 21, 2013, issue of the British Journal of Haematology.

Myelofibrosis is commonly diagnosed in people between the ages of 60 and 70, and affects approximately one-to-two out of every 100,000 people in the United States annually. The disorder is characterized by anemia, fatigue, bone or joint pain, and an enlarged liver and spleen. Survival usually is between five and seven years, but some patients develop acute leukemia, which can limit survival to three-to-five months.

According to Drs. Hoffman and Mascarenhas, who designed and ran the trial, persistence and ingenuity paved the way for their findings. Signs of significant improvement appeared a year after patients were started on an oral regimen of low-dose panobinostat. “We have patients who are doing well after two-to-three years, and whose survival was predicted to be on the order of months,” says Dr. Mascarenhas.

The key to success was maintaining a low dosage. Interestingly, too high a dosage of panobinostat would have produced toxicity forcing patients to drop out of the trial before positive results could be seen, says Dr. Mascarenhas.

“Persistence led us to finally see signals of activity,” Dr. Mascarenhas recalls. “One of our patients came in for a checkup and her blood smear looked normal. I gave it to Dr. Hoffman to look at and asked him what he thought was wrong with the patient. He said, ‘Nothing. It’s normal.’ Then I told him it was one of our patients in the trial.”

To date, the only potentially curative treatment approved for people with myelofibrosis is a bone marrow transplant. But elderly patients or those with comorbidities are not eligible for transplants, and a suitable bone marrow donor is not always available.

Drs. Hoffman and Mascarenhas have now initiated a new phase I clinical trial that will combine lower doses of panobinostat with ruxolitinib, a drug manufactured by Incyte Pharmaceuticals that has been approved by the U.S. Food and Drug Administration to treat the symptoms of myelofibrosis.

This article was first published in Inside Mount Sinai.