Researchers at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai have demonstrated the potential for a new combination therapy to improve outcomes for patients with myelofibrosis, a rare and aggressive blood cancer. The phase 3 trial, published this month in Nature Medicine , represents the first randomized study of JAK inhibitor-based combination therapy in treatment-naïve myelofibrosis patients, signaling a major advancement in disease management.
The study, led by John Mascarenhas, MD, Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai, is the first major study to test a combination of two medicines to treat myelofibrosis, instead of using one at a time. The trial evaluated the efficacy and safety of pelabresib plus ruxolitinib in patients newly diagnosed with myelofibrosis. The findings suggest that combining these targeted therapies results in deeper clinical responses, with the potential to modify the disease course and improve overall survival.
"We are hopeful that this study will mark the beginning of a new era in myelofibrosis treatment," said Dr. Mascarenhas. "For too long, patients have relied on single-agent JAK inhibitors that, while beneficial, fail to modify the disease course for most individuals. Our findings highlight the power of rationally designed combination therapies to deliver deeper and more durable responses."
According to the American Association for Cancer Research, there are an estimated 13,000 people living with myelofibrosis in the United States. Myelofibrosis patients who fail monotherapy treatments typically experience poor outcomes within two to three years. This study suggests that combination therapy could lead to longer-lasting responses, improved disease control, and potentially extended survival.
The data from this trial could lead to regulatory approval of combination therapy, establishing a new standard of care for early myelofibrosis management. The study's robust correlative analyses further support the potential of this combination to alter disease progression, offering hope for patients who currently face a median survival of just five years.
Next, the research team will continue to monitor patients for long-term survival outcomes. Additional data from the study will be presented at the European Hematology Association meeting in June 2025 and at the American Society of Hematology conference in December, providing further insights into the therapy's long-term benefits.
The study was conducted across 80 medical centers worldwide and funded by MorphoSys Pharmaceuticals.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City's large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master's degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 500 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
