Since 2011, CR&T has committed $6.5 million to the Richard T. Silver Myeloproliferative Neoplasms (MPN) Center at Weill Cornell Medicine in New York City. Our goal is to sustain the Center’s role as a world-class leader in research, treatment, and care for people with these blood cancers. Below, we focus on key MPN studies presented by Silver Center investigators at the Annual Meeting of the American Society of Hematology (ASH), which took place in December 2019 in Orlando, FL. Researchers will continue to build on this important work in the year ahead.
Highlights of the ASH Annual Meeting
Exploring the Role of Interferon
Interferon-alpha (IFN-alpha) is the only drug that can reverse the progression of MPNs. Research has shown that this drug can reduce fibrosis (scarring) in the bone marrow and alleviate symptoms. Richard T. Silver, MD, CR&T’s Vice President and Medical Director, has conducted pioneering research into the use of interferon in the MPNs, and for many years, was one of the few investigators to focus on the drug. Today, Dr. Silver is joined by many other investigators worldwide who are exploring the role of IFN-alpha in treating the MPNs. These include Andrew I. Schafer, MD, the Silver Center’s Director; Joseph M. Scandura, MD, PhD, its Scientific Director; Ghaith Abu Zeinah, MD, Instructor in Medicine; and associated research assistants, technicians, and nurses.
Two important studies by these investigators and their colleagues focused on the effectiveness of IFN-alpha as a treatment for polycythemia vera (PV), one of the MPNs. One study showed, for the first time, that IFN-alpha lowers PV patients’ risk of developing myelofibrosis, which causes scarring of the bone marrow and is the most serious form of MPN. Further, the drug enables these patients to live longer than those receiving other standard MPN therapies. Using computer-based information retrieval systems developed with Dr. Scandura’s input, this study analyzed the records of 306 PV patients treated at Weill Cornell Medicine from 1974-2019. It is the largest study with the longest follow-up of PV patients treated with IFN-alpha.
PV patients are also at risk for developing blood clots (thrombosis). This is because the disease causes the bone marrow to make too many red blood cells, which thickens the blood. Serious complications, such as splanchnic vein thrombosis (blood clots in the abdominal veins), stroke, and deep vein thrombosis (blood clots in the body’s deep veins, especially in the legs) can occur.
Another large study by Silver Center researchers showed that interferon is more effective in reducing the risk of thrombosis than other standard treatments such as chemotherapy and bloodletting (phlebotomy).
These studies would not have been possible without the Silver Center’s extensive patient database, which was developed with CR&T funding. We are grateful to The Applebaum Foundation for its generous support of this research, including the development of the database.
Potential Treatment for Anemia in MPN Patients
Because of fibrosis (scarring) in the bone marrow, many people with MPNs suffer from chronic anemia, which is difficult to treat. This may be due to an excess of the protein TGF-beta in the marrow. Researchers believe that, in addition to suppressing red blood cell production, TGF-beta causes the scarring in myelofibrosis. Silver Center investigators, led by Dr. Scandura, were able to block the production of TGF-beta in mice. Next, they gave the mice a tiny dose of the hormone erythropoietin, which stimulated red blood cell production. Based on these findings, the researchers have received funding for a clinical trial that could lead to the development of a more effective treatment for anemia in MPN patients.
Ruxolitinib and Weight Gain
In the February 2020 issue of Blood, a paper written by Dr. Scandura and Silver Center colleagues was published, reporting on the results of an important study on the cause of weight gain in MPN patients who are taking the drug ruxolitinib.
Many people with PV or myelofibrosis have benefited from ruxolitinib. However, researchers found that some patients taking the drug gained considerable weight and that their cholesterol was elevated – a serious concern in patients who are already at a higher risk for cardiological complications. The Silver Center team’s goal was to identify those patients who were most likely to gain weight and to pinpoint the underlying cause of this weight gain.
Through their analysis of a mouse model, the researchers discovered that ruxolitinib blocks a hormone called leptin, which helps control appetite. Because their bodies don’t signal that they are full, some patients are always hungry, which leads to significant weight gain. Based on their analysis of 179 patients, the investigators were able to predict which patients had the highest risk of gaining weight. They found that those who gained more than two percent of their pre-treatment weight within 60 days of starting treatment with ruxolitinib were more likely to continue gaining weight, to increase their body mass index (BMI), and/or to become overweight. Armed with this information, physicians can provide dietary counseling and recommend lifestyle changes that will help these patients to control their weight early on.
Launching new clinical trials is key to the discovery of effective new treatments for these blood cancers. The Silver MPN Center conducts clinical trials in collaboration with major pharmaceutical partners, which are attracted by the expertise of the Center’s staff and by its strong infrastructure, which allows for highly targeted and rapid recruitment of patients that meet the study criteria.
For information about studies that are now seeking participants, please visit https://silvermpncenter.weill.cornell.edu/research-and-clinical-trials/myeloproliferative-clinical-trials