December 09, 2002

Jane Salodof MacNeil

Dec. 9, 2002 (Philadelphia) — Five patients with advanced, treatment-resistant leukemia are in complete remission after receiving a new experimental peptide vaccine in a pilot study that was only intended to determine whether the vaccine is safe.

The longest-lasting survivor has lived more than two years with sensitized T-cells still circulating in the patient's blood stream, according to principal investigator Jeffrey R. Molldrem, MD, a researcher at M.D. Anderson Cancer Center in Houston, Texas.

Dr. Molldrem presented phase I results for the vaccine, PR1 peptide, here at the American Society of Hematology (ASH) annual meeting. His report is the first evidence that a peptide vaccine can immunize leukemia patients against remission.

Three of the patients had failed therapies for chronic myeloid leukemia (CML). One had not responded to treatment for acute myelogenous leukemia (AML), and the fifth had myelodysplastic syndrome (MDS).

Carl H. June, MD, professor of pathology and laboratory medicine at the University of Pennsylvania in Philadelphia, underscored the importance of the PR1 breakthough by looking back at the long, frustrating efforts to engage the immune system against cancer. "The holy grail has been to develop a vaccine to prevent and treat cancer," he told attendees of a plenary session. "Yet after a century of research there are no FDA-approved cancer vaccines."

Dr. Molldrem and his colleagues have already opened a phase II trial, which could take six months to a year to complete, depending on how fast they can enroll 60 patients for the study.

"The results are very exciting, but we are very cautious about them," he said at a press conference yesterday, noting that only 15% to 20% of CML patients are disease-free 10 years after standard treatments.

Dr. Molldrem's group tested the vaccine in nine patients — four with AML, four with CML, and one with MDS. He said the participants had failed multiple therapies, including one patient who had tried imatinib mesylate (Gleevec) and several who had undergone bone marrow transplants.

Eight patients (54%) responded to the vaccine, producing T cells primed to attack a nine-amino acid chain derived from proteinase 3. The researchers chose proteinase 3 because it is overexpressed in leukemia cells and can serve as a marker for T cells to recognize and attack.

Although proteinase 3 is present in lower concentrations in normal cells, Dr. Molldrem said no T cells primed by the vaccine have attacked normal cells.

The phase II trial will continue to give the vaccine in the three dose levels used in the initial study — 0.25 mg, 0.5 mg, and 1.0 mg, injected once a week for three weeks. Patients responded at all three dose levels, so no single dose has emerged as optimal, according to Dr. Molldrem. The patients also received 75 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Adverse effects were minor, Dr. Molldrem said, consisting mainly of low-grade fever and a small rash at the injection site. Two AML patients have since died of advanced disease.

The peptide chosen for the initial vaccine is effective only in patients who are HLA-A2 positive. Dr. Molldrem said this is the most common human leukocyte antigen, present in about 40% of the general population. Ultimately, he suggested, investigators will be able to develop vaccines to cover the rest. If the PR1 peptide vaccine works, they will be able to follow a similar strategy with other peptides, he said.

In a prepared statement, ASH president Robert I. Handem, MD, said the study was very important despite the small number of participants. "Investigators have struggled very hard to develop effective immunotherapy for any malignancy," he said. "These results in leukemia are very encouraging and may be an important step forward."

ASH 44th Annual Meeting: Abstract 8. Presented Dec. 8, 2002.

Reviewed by Gary D. Vogin, MD

Jane Salodof MacNeil is a freelance writer for Medscape.

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