Dr. Raajit Rampal studies myelofibrosis in the lab and in the clinic.
An international phase 3 clinical trial of a new drug combination for treating the blood cancer myelofibrosis found that adding a second, experimental drug to standard treatment was more effective than the standard treatment alone. Further, adding the second drug did not significantly increase side effects. Memorial Sloan Kettering Cancer Center (MSK) enrolled the most patients in the trial.
“This is one of the largest myelofibrosis clinical trials to date,” says MSK leukemia specialist Raajit Rampal, MD, PhD, lead author of the study, published March 10 in Nature Medicine. “There is a real unmet need for patients with this disease, and the findings from this trial represent an exciting advance.”
This study looked at adding an experimental drug called pelebresib to the drug ruxolitinib (Jakafi®), which is the current treatment for myelofibrosis. Both drugs are targeted therapies. Pelebrisib blocks the action of proteins involved in inflammation and cancer; ruxolitinib blocks a protein called JAK. This combination approach was based on ongoing research from the lab of MSK leukemia specialist and physician-scientist Ross Levine, MD.
What Is Myelofibrosis?
Myelofibrosis is a rare form of blood cancer called a myeloproliferative neoplasm. It is characterized by a buildup of scar tissue (called fibrosis) in the bone marrow. It affects about 20,000 people in the United States.
“Myelofibrosis is considered a progressive disease, which means it continues to worsen over time,” Dr. Rampal says. “In many people, it eventually transforms into full-blown leukemia.”
The most common symptoms of the disease are:
- an enlarged spleen and liver
- anemia (low red blood cell counts)
- extreme weight loss
Patients with myelofibrosis also have high levels of proteins called cytokines in their blood — a sign of severe inflammation.
How Is Myelofibrosis Treated?
Until 2011, when ruxolitinib was approved by the U.S. Food and Drug Administration (FDA), there were no good treatments for myelofibrosis. Ruxolitinib offers symptom relief for some patients, but it is not a cure. Additionally, it eventually stops working for most patients.
“The approval of ruxolitinib was an important advance for patients, but it’s been clear that more progress is needed,” Dr. Rampal says.
Pelabresib-Ruxolitinib Clinical Trial Results
The new study was a double-blind, placebo-controlled trial that enrolled 430 patients. All of them were newly diagnosed and had not received any previous treatment.
- About half received the pelabresib-ruxolitinib combination.
- The rest received ruxolitinib plus a placebo.
- Both drugs are taken as pills.
The treatment’s effectiveness was measured primarily by how much the patients’ enlarged spleens shrank.
- Nearly 66% of patients in the combination group had significant shrinkage versus about 35% of those who got standard therapy.
Patients who received the experimental therapy also experienced lower levels of inflammatory cytokines. In addition, their bone marrow appeared to be healthier. “This is a strong indication that the drugs were having a biological effect on the cancer cells,” Dr. Rampal says.
The side effects were about the same in the two groups. The most common were reduced red blood cells and platelet counts. Only one side effect was worse in the patients who received pelabresib — a change in the sense of taste, which was improved by lowering the drug dosage.
The History of Lab Research Leading to Improved Patient Care
Dr. Rampal says the development of both ruxolitinib and pelabresib would not have been possible without years of research in Dr. Levine’s lab, including studies done on mouse models of myelofibrosis.
“This is such a clear example of the importance of bench to bedside research,” Dr. Rampal notes. “Our discoveries in the lab have really guided this work, which has already helped so many and will continue to benefit more patients in the future.”
