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LRF Career Development Award Recipient Lauded for Successful Mantle Cell Clinical Trial

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Joshua Brody, MD (Instructor, Division of Oncology, Department of Medicine, Stanford University School of Medicine) has found much success since his clinical trial studying the efficacy of immunotherapy in mantle cell lymphoma (MCL) commenced two years ago. After being awarded with the Lymphoma Research Foundation Clinical Investigator Career Development Award in 2007, Dr. Brody was able to apply his pre-clinical research in cancer vaccines to his current trial. The study protocol has shown significant positive effects on treatment of the disease and Dr. Brody and his team have been lauded by both the American Society of Clinical Oncology (ASCO) and the Swiss Cancer League. He will present the results of his trial thus far at both organizations’ meetings this month.

The results Dr. Brody plans to present at ASCO and the Swiss Cancer League meetings are preliminary, but show significant achievement. The initial goal of the study was to gauge anti-tumor immune response by answering the question: “Does immunotransplant amplify the proportion of patients’ anti-tumor T-cells compared to vaccination alone.” Dr. Brody had planned to enroll only 30 patients and declare success if he found this amplification in a significant number of those 30. Instead, early on in the trial, he noticed the amplification in almost every patient tested.

A patient-specific or custom-made cancer vaccine is an immunological treatment based on the genetic makeup of an individual patient’s tumor. Traditionally, these personalized vaccines are non-toxic and routinely given to a patient during a period of minimal disease—for example, after the patient receives chemotherapy. The vaccine works by enlisting a patient’s own immune system to attack the cancer. Many researchers have been studying these type of cancer vaccines, but have had mixed results.

Under the guidance of Ronald Levy, MD (Professor and Chief, Division of Oncology, Stanford University School of Medicine), Dr. Brody and his colleagues have been testing a new method for administering vaccines that gives a patient the vaccine after he or she has received chemotherapy and an autologous stem cell transplant (ASCT).

With this new treatment protocol, patients undergo a biopsy to obtain tumor cells that will be used to develop the vaccine. After the biopsy, patients receive chemotherapy followed by a preliminary vaccine. The body’s immune system responds to this preliminary vaccine by producing anti-lymphoma immune cells (primed T-cells) that are harvested from the patient’s body two weeks later, using a medical technique called leukapheresis, and frozen. Patients then receive high-dose chemotherapy and an ASCT.

According to Dr. Brody, this is an ideal time to administer a vaccine since the chemotherapy has destroyed the majority of lymphoma cells, as well as the body’s immune cells. “At this point, the patient’s immune system is a clean slate and if vaccinated against cancer now, the immune system has the opportunity to re-grow as an anti-cancer immune system,” Dr. Brody said.

To destroy any remaining residual lymphoma, patients receive an infusion of the vaccine along with some of their previously harvested anti-lymphoma immune cells after the ASCT. Booster doses of vaccine are also given three months post-ASCT.

With 24 patients from across the country enrolled in the trial only 21 months after it began, Dr. Brody and his team have doubled their anticipated accrual rate and he believes this is partially attributable to LRF’s clinical trials information service.

At this point, the trial protocol has been expanded to include about 60 patients and further investigate the proportion of patients maintaining a “molecular remission” at one-year post-transplant. The question Dr. Brody now looks to answer is: “Is the one-year molecular remission rate after immunotransplant superior to that seen in two large trials (Scandinavian and German) of standard autologous transplant for MCL?

Dr. Brody’s work with individualized vaccines was validated by the greater lymphoma community this year when he was asked to present at the 2011 ASCO Annual Meeting in Chicago, Illinois and the International Conference on Malignant Lymphoma in Lugano, Switzerland. Along with these presentations, he was honored with a prestigious ASCO Merit Award and a Swiss Cancer League/Swiss Academy of Medical Sciences Grant.

“ASCO is first and foremost a forum for presentation of results of immediate clinical relevance,” Dr. Brody said. “Therefore, receiving the Merit Award is extremely gratifying in that it suggests that our results, while already interesting from the perspective of basic tumor immunology, are sufficiently encouraging that they might one day impact our clinical practice. We hope that this recognition will give us the opportunity to make more oncologists aware of the immunotransplant approach and bring this therapy to a greater number of MCL patients throughout the U.S.”

Grateful to LRF for providing him with the funding to launch this trial, Dr. Brody said his grant helped him meet and exceed his expectations of how his career in lymphoma research would begin.

“LRF’s Career Development Award allowed us to perform the pre-clinical studies that were the basis of, and justification for, the clinical trial,” he said. “We envisioned initiating the trial, but didn't predict that the patient accrual would be as rapid as it has been or that the amplification of anti-tumor immunity would be as remarkable as what we have seen. Without the award, we likely would not have been able to justify and initiate the trial, so it was absolutely crucial in that respect.”

He further stressed the importance of continuing support from non-profit research organizations for future advancement of lymphoma research.

“For many novel therapies being developed to treat patients with cancer, funding depends heavily on industry,” he said. “For certain types of therapy, such as improvements to stem cell transplant and other personalized cellular therapies the physician/scientists developing these approaches depend on funding from the NIH and philanthropic organizations such as the LRF. We're hopeful that our work will show that investment in such organizations can yield real benefits to patients in the near-term.”

June 15, 2011

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