In study results published online today in Blood, the Journal of the American Society of Hematology (ASH), investigators at Weill Cornell Medical College provide the very first long-term outcome data for patients with chronic ITP treated with rituxamab.
Approximately 200,000 Americans suffer from ITP, a bleeding disorder in which the immune system destroys blood cells called platelets that are necessary for normal blood clotting, which can result in excessive bleeding and heavy bruising. Common treatment options for increasing platelet counts in the majority of patients with ITP include corticosteroid drug therapy, used to suppress a patient’s immune system in order to help bring platelet counts back to normal; splenectomy, the surgical removal of the spleen, to halt the destruction of antibody-coated platelets found in the organ; and newer thrombopoietin (TPO)-mimetic agents to help stimulate platelet production. While these treatments are successful in many patients, all are associated with side effects: corticosteroids are associated with bone loss, cataracts, and other serious toxicity with long-term use; splenectomy can increase a patient’s risk of infection; and TPO-mimetic agents can result in blood clots; and their long-term response in patients is not well-studied. In addition to their reported side effects, some patients with ITP stop responding or have insufficient response to these therapies.
More than ten years ago, researchers identified rituximab as an alternative treatment for patients with chronic ITP who have failed at least one other therapy. Rituximab specifically destroys B-cells — the cells responsible for producing antibodies that coat platelets and lead to their destruction — with low toxicity and decreased risk of infection compared to other treatments. Previous studies have shown that rituximab treatment resulted in normalized platelet counts lasting longer than one year in some patients with chronic ITP. Despite these encouraging reports, long-term data were previously lacking, and the durability and long-term safety of this treatment were largely unknown.
“While rituximab therapy for chronic ITP has been an exciting development, until now, due to a lack of sufficient patient numbers and follow-up in previous studies, we have only known how this treatment will affect ITP patients in the short term,” says Vivek L. Patel, PhD, the study’s first author and research associate at Weill Cornell Medical College in New York. “By utilizing the longest follow-up and the largest number of responders to the drug, our study sought to determine how children and adults with chronic ITP treated with rituximab would fare three, four and five years down the road.”
In this follow-up study, Dr. Patel’s team reviewed 18 published clinical trials assessing rituximab treatment in children and adults with ITP and calculated initial and one-year response rates for 138 patients treated in 2000–2007 from seven clinical centers in the United States and Europe. Seventy-two adults with ongoing response one year from first treatment and 66 children with partial or complete response of any duration were included in the long-term analysis. The investigators calculated five-year response rates of 26 percent for children and 21 percent for adults. The researchers also analyzed the relationship of other clinical variables in response to rituximab and found no difference in projected five-year outcomes in children and adults who had undergone prior splenectomy versus those who had not. Age, gender, prior ITP duration and response to other ITP treatment were also not predictive of duration of response.
Results are particularly encouraging for ITP patients and their physicians who now have more substantial long-term data to help them decide whether and when to treat with rituximab. “The results from this study provide clinicians and patients with accurate and realistic expectations of the long-term effect of rituximab and its potential to become a first-line treatment for ITP,” says James B. Bussel, MD, senior author and professor of pediatrics and professor of pediatrics and obstetrics and gynecology at Weill Cornell Medical College, and a pediatrician at the Komansky Center for Children’s Health at NewYork-Presbyterian/Weill Cornell. “Our next step is to try to augment the effect of rituximab by combining it with dexamethasone, a common steroid therapy for ITP, in order to determine its effect in conjunction with known treatment strategies.”
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University’s medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson’s disease, and most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.