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Immune-Based Lymphoma Treatment Shows Promise

Similar patient-tailored approaches may work for skin, stomach and other cancers, researchers say

SUNDAY, May 31 (HealthDay News) -- In a new study, patients with follicular non-Hodgkin lymphoma who received a vaccine made from their own cancer cells went more than 44 months before relapsing, compared to only 30.6 months for those who didn't get the vaccine.

The vaccine trial was one of several studies from the new frontier of "personalized medicine" presented Sunday at the American Society of Clinical Oncology (ASCO) annual meeting, in Orlando, Fla.

The approach aims to hit cancer hard by tailoring treatments to the patient's own genetics or disease, among other factors.

The lymphoma study differs from other vaccine trials in that the tool was patient-specific, study author Dr. Stephen Schuster, an associate professor at the University of Pennsylvania School of Medicine, explained at a Sunday news conference.

The findings could signal a whole new direction in how vaccines are used against cancer, experts said.

"The novelty of the vaccines is that they were individualized to each patient, and that they were directed against a cancer-specific target," said Dr. Louis Weiner, director of Georgetown's Lombardi Comprehensive Cancer Center in Washington, D.C. "Many vaccines are directed against cancer-associated targets and always run the risk of damage to normal cells."

But the lymphoma vaccine is "almost like an immune-system 'smart bomb,'" Weiner noted. "It only goes after malignant cells, and that's very attractive."

For this phase III trial, 76 patients who had been in remission for at least six months following chemotherapy were injected with BiovaxID, a vaccine engineered from cancerous tissues drawn from each individual patient. The mixture also contained compounds designed to heighten the effect of the vaccine.

These individualized vaccines took about three months to develop. Each patient received five injections over six months.

"The vaccine targets the 'idiotype' protein on the cell surface [of cancerous B cells in follicular lymphoma]. The protein is unique to cancer cells and varies from patient to patient," Schuster explained. "The idiotype vaccine with the immune stimulatory molecules improved disease-free survival following chemo."

However, in contrast to other phase III trials involving cancer vaccines, "remission before receiving the vaccine might be a prerequisite for deriving benefit, or at least statistically significant benefit," he added.

Another phase III trial for another cancer vaccine -- this one for advanced melanoma -- also produced promising results, marking the first evidence of clinical benefit of vaccination in patients with melanoma.

This time, researchers added a new cancer vaccine, called gp100:209-217(210M) peptide, to conventional therapy.

"In the past, what we've tried to do in the cancer immunology field is to attack tumors one agent at a time. Now we're starting to combine agents together for effective therapy," said study senior author Dr. Patrick Hwu, melanoma chief at the University of Texas M.D. Anderson Cancer Center in Houston. "Our approach here was to combine the vaccine with interleukin 2 to get immune cells to attack the tumor. All immune approaches try to get killer T-cells to attack the tumor. The vaccine allows the 'soldiers' to go through boot camp, [it] initiates the training of soldiers. The soldiers then multiply into a large army that can then attack tumors to kill them."

Patients receiving the vaccine had longer overall survival -- 17.6 months vs. 12.8 months for controls -- but that was not considered statistically significant. They also experienced a progression-free survival of 2.9 months vs. 1.6 months for those who didn't get the vaccine. Better still, 22 percent saw their tumors shrink, as compared with only 9.7 percent in the chemo group.

"This is amongst the first trials to show that cancer vaccines can be effective in patients," Hwu said. "This is the deadliest of skin cancers and, when it metastasizes, the median survival is less than a year. We sorely need new approaches."

"This is the first prospective randomized trial of this combination," said Dr. Margaret von Mehren, a medical oncologist with Fox Chase Cancer Center in Philadelphia. "What struck me was the six-month survival difference between the two groups. That's a really long time for metastatic melanoma."

Also at the meeting, researchers showed for the first time that trastuzumab (Herceptin) -- a highly targeted biological drug widely used to treat certain kinds of breast cancer -- may also effective in patients with advanced gastric or stomach cancers who also take chemotherapy.

"This is the first biological to show a survival benefit in an advanced gastric cancer," said study author Dr. Eric Van Cutsem, a professor with University Hospital Gasthuisberg in Leuven, Belgium. "It reduced the risk of death by 26 percent."

Herceptin targets the HER2 receptors that are found on breast cancer cells in about a quarter of patients. In this trial, the same receptor was spotted on malignant cells in about 22 percent of gastric-cancer patients, the team said.

People receiving Herceptin lived a median of 13.8 months vs. 11.1 months for those receiving chemo alone. According to Cutsem, patients with advanced stomach cancer typically only live a median of nine to 11 months.

He recommended testing for HER2 in gastric cancer patients right away. Rather than simply repeating the same trial, he pressed for trials exploring new and different ways to use the drug.

"This is an extremely important study showing that, for a significant minority of patients, the first non-cytotoxic therapy to have any kind of effectiveness against this type of cancer," said Dr. Sonali Smith, an associate professor of medicine at the University of Chicago Medical Center, who moderated the press briefing. "I would consider this extremely promising, and repeating this study is not helpful to patients.

And in yet another example of more targeted, personalized cancer care, scientists in France reported on a possible biomarker -- a protein known as MSH2 -- that might predict which patients with non-small cell lung cancer will fare better on cisplatin-based chemotherapy.

MSH2 is one of a family of DNA repair genes, the irony being that the gene also repairs DNA purposely damaged by chemotherapy. Not surprisingly, then, patients with either low levels of MSH2 or none at all respond better to cisplatin treatment than patients with higher levels.

"The findings duplicate those of a prior study that showed similar results with a different DNA repair gene, ERCC1," noted Dr. George Simon, director of the thoracic oncology program at Fox Chase Cancer Center in Philadelphia. "When these two genes are taken in combination, they seem to predict better than ERCC1 alone."

More information

Find out more about more targeted cancer care at the Personalized Medicine Coalition.

SOURCES: Louis M. Weiner, M.D., director, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C.; George Simon, M.D., director, thoracic oncology program, Fox Chase Cancer Center, Philadelphia; Margaret von Mehren, M.D., medical oncologist, Fox Chase Cancer Center, Philadelphia; May 31, 2009, news conference with Sonali Smith, M.D., associate professor, medicine, University of Chicago Medical Center; Stephen J. Schuster, M.D., associate professor, University of Pennsylvania School of Medicine, Philadelphia; Eric Van Cutsem, M.D., Ph.D., professor, University Hospital Gasthuisberg Leuven, Belgium; Patrick Hwu, M.D., melanoma chief, University of Texas M.D. Anderson Cancer Center, Houston, American Society of Clinical Oncology annual meeting, Orlando, Fla.

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