Immunotherapy Benefits Children With High-Risk Sarcomas

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Title: Immunotherapy Benefits Children With High-Risk Sarcomas
URL: http://www.pslgroup.com/dg/226C9E.htm
Doctor's Guide
August 1, 2008

PHILADELPHIA -- August 1, 2008 -- Immunotherapy could prove beneficial in treating high-risk forms of paediatric sarcomas, according to a pilot study published in the August 1 issue of Clinical Cancer Research.

Researchers from the US National Institutes of Health, Bethesda, Maryland, tested a novel dendritic vaccine, as well as a standard flu vaccine, to potentially strengthen the immune system of children postchemotherapy.

Their findings showed that although the dendritic vaccine did not perform as well as expected, children responded well to the standard flu vaccine, suggesting that a strategy to bolster immune function in these patients holds promise for fighting their cancer.

Researchers also found that survival in these patients was at the higher end of what is generally seen with recurrent and/or metastatic Ewing's sarcoma [family tumour] (ESFT) or alveolar rhabdomyosarcoma (AR).

Patients who did not receive immunotherapy (n = 22) had a 5-year overall survival of 31%, compared with a 5-year survival of 43% in patients who ultimately received the novel immunotherapy (n = 30).

Although the study was small, these early findings are promising, according to senior investigator Crystal Mackall, MD, Pediatric Oncology Branch, US National Cancer Institute, Bethesda, Maryland.

"We need new therapies. While outcomes overall for these tumours have improved during the past 40 years, there has not been substantial improvement for patients with metastatic or recurrent disease," said Dr. Mackall.

"This study shows that immunotherapy is safe and well tolerated and could ultimately be beneficial for this high-risk population."

"We now know that the immune system of patients recovering from chemotherapy is malleable, so we just need to find the best immunologic approach to exploit this window of opportunity," she said.

For the study, researchers attempted to use immunotherapy as consolidation therapy. Patients (N = 52) underwent aphaeresis to harvest blood lymphocytes that were then frozen. From this, dendritic cells were later extracted.

All patients then had chemotherapy, radiation, or surgery, as appropriate, and in some cases a stem cell transplant to induce remission. The 30 patients who initiated immunotherapy received a common flu vaccine as well as their own lymphocytes and their own dendritic cells. Some patients also received interleukin-2.

"The good news was the surprisingly nice T-cell response patients had to the flu vaccination, even relatively soon after completing chemotherapy," said Dr. Mackall.

"That shows that the general idea of using immunotherapy following chemotherapy to prevent recurrence is not a flawed one. Chemotherapy depleted the immune system, but we could restore it."

The authors acknowledge that much further research is needed to optimise the dendritic vaccine, which was not very immunogenic. "Current studies are underway to test a new version of the vaccine, which utilises more mature dendritic cells and tumour lysate in lieu of the translocation peptides," said Dr. Mackall.

Dr. Mackall also notes that the vaccine in this trial was tested in patients whose cancer had recurred or metastasised. If the favourable safety profile continues and the efficacy of the vaccine is improved with the subsequent versions, one could ultimately consider the use of immunotherapy to consolidate remission in lower risk populations.

SOURCE: American Association for Cancer Research

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