(ORLANDO) – Although the majority of patients with follicular lymphoma initially respond to chemotherapy, the disease frequently recurs, eventually becoming resistant to available therapies. Patients treated with traditional chemotherapy followed by a personalized vaccine were found to have a 44 percent increase in progression-free survival compared with patients who responded to chemotherapy but received a control vaccine, according to research from the University of Pennsylvania School of Medicine.
Stephen J. Schuster, MD, associate professor in the division of Hematology/Oncology at Penn’s Abramson Cancer Center, presented the results of the randomized, double-blind, phase III clinical trial yesterday at the annual meeting of the American Society of Clinical Oncology (ASCO).
Patients who had a complete remission after chemotherapy lasting longer than six months received a vaccine prepared from their own freshly isolated tumor cells. Patients treated with the tumor-derived vaccine had a median time to relapse of 44.2 months compared with 30.6 months for patients treated with the control vaccine.
The personalized vaccine used in the current study included tumor-derived idiotype protein – a protein unique to each lymphoma tumor – that is isolated from individual patient samples and linked to the hemocyanin protein from the keyhole limpet. It is injected simultaneously with an immune-stimulating agent called GM-CSF. The control vaccine included the keyhole limpet hemocyanin protein plus GM-CSF.
Although idiotype vaccines have been tested previously, this is the first trial to show a statistically significant improvement in progression-free survival in follicular lymphoma patients treated with an idiotype vaccine. Previous trials included patients who had partial or complete responses, whereas this trial only vaccinated patients who had no detectable tumor remaining after chemotherapy. Under these conditions, the investigators hypothesized that the vaccine could hold minimal residual disease in check.
“Whether the vaccine eradicated the disease that could no longer be seen on CT scan for patients in remission or just controlled minimal residual disease, remains to be determined,” Schuster says. “Even slowing the recurrence rate would be an amazing achievement because, in this study, we used this vaccine to improve patient outcomes after a single series of immunizations, and many vaccines require booster shots, which were not part of the original trial.”
When the trial started, chemotherapy was the standard of care for previously-untreated patients. Since that time, the standard of care has evolved to include chemotherapy plus the antibody rituximab (Rituxan®). Therefore, Schuster thinks a clinical trial should be launched to test whether adding a personalized vaccine to the current standard of chemotherapy and rituximab will improve patient outcome. “If indeed our trial is right that this approach leads to improvements in progression-free survival, then adding it to even more effective therapies like chemotherapy plus Rituxan®, might result in even greater benefit,” Schuster says. “Combination therapies have been the paradigm in oncology resulting in greater successes with successive generations of therapies and cures for certain cancers.”
Although both rituximab and the tumor vaccine tested in this trial are immunologic agents, they work by different mechanisms. Rituximab is a mass-produced antibody designed to attack the type of cell that has gone awry in follicular lymphoma. By contrast, the newly-tested personalized vaccine induces the patients’ own immune systems to attack their tumors based on a protein that is uniquely expressed by their tumor cells.
In addition to the immediate clinical results, the trial will provide an important opportunity for biomarker discovery in the future. Tumor samples were collected from all of the patients who enrolled in the trial. “This is a treasure trove of material,” Schuster says. “It is a rare opportunity to have outcomes data with the corresponding banked viable tumor cells and tumor infiltrating cells present for analysis. This is an opportunity for learning that cannot be passed up.”
PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to the National Institutes of Health, received over $366 million in NIH grants (excluding contracts) in the 2008 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center, named one of the nation’s “100 Top Hospitals” for cardiovascular care by Thomson Reuters. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.
The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, composed of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 400 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.