Jason Weiner has benefited from the opportunity to participate in a myelofibrosis clinical trial at MSK. He is shown here with his wife, Cori, children Dominik, Kasia, and Damian, and dog Babka around the time he first enrolled in the study.
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, 2025, 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 pelabresib to the drug ruxolitinib (Jakafi®), which is the current treatment for myelofibrosis. Both drugs are targeted therapies. Pelabresib 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. It’s an example of how painstaking, persistent work in a lab over decades can result in new treatments for patients.
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.
Jason’s Experience in a Myelofibrosis Clinical Trial
One MSK patient to benefit from this trial was Jason Weiner, an attorney, husband, and father of three teenagers.
Now 53, Jason had been diagnosed with another blood disorder, called polycythemia vera, when he was in his mid-20s. The drug interferon had kept his disease under control for decades, but in 2021 regular blood work revealed that the polycythemia vera had progressed to myelofibrosis. “My biggest concern was that the myelofibrosis would convert to leukemia,” he says. “I wasn’t even feeling sick, but I wanted to stop it right away.”
Jason, who was living in Alaska at the time, knew it would be difficult to find care close to home. So he searched the rest of the country for the top experts in myelofibrosis. His research led him to Dr. Levine and Dr. Rampal. As a New York native who still has family in the area, he knew MSK’s reputation for cancer care.
How Is Myelofibrosis Treated?
The standard treatment for myelofibrosis since 2011 has been ruxolitinib, which relieves symptoms for some people but is not a cure. It eventually stops working for most patients.
When Dr. Rampal explained the treatment options and gave Jason the opportunity to enroll in the myelofibrosis trial, he was eager to participate — even though it would require frequent travel. In the beginning, he had to come to New York every three weeks for tests.
Pelabresib-Ruxolitinib Clinical Trial Results
Jason was one of 430 patients participating in the double-blind, placebo-controlled trial. All were newly diagnosed and had not received any previous treatment for myelofibrosis.
- 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.
Side Effects of New Myelofibrosis Treatment
The side effects were about the same in the two groups. The most common ones were reduced red blood cell and platelet counts.
“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,” says Dr. Raajit Rampal.
Only one side effect was worse in the patients who received pelabresib: a change in the sense of taste. Jason says in the beginning it was difficult to deal with the bad taste in his mouth, but he found coping techniques, such as regularly sipping water with electrolytes and cranberry juice. He no longer has issues with taste.
He benefited from the drug combination right away. “Within three weeks, my spleen, my blood counts, everything in my body normalized,” he says. “This treatment really has done wonders.”
Jason and his family recently moved to Maine. There, they have been able to continue the active lifestyle they lived in Alaska, including skiing. “I really have no limitations on what I can do,” he says. “I feel better now than I did all the years I was getting interferon.” He continues to take the pelabresib-ruxolitinib combination daily.
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.”
Jason is enthusiastic about the promise of this treatment. “I was one of the younger people in this trial, and because I wasn’t yet very sick when I started, I really gained a lot,” he says. “I hope this drug will be available to more people earlier in the course of disease, when they have the greatest likelihood for improvements.”
