Leukemia vaccine triples event-free survival

December 11, 2007

NEW YORK (Reuters Health) - A peptide vaccine against leukemia-associated antigens more than triples event-free survival, from 2.4 months with conventional therapy to 8.7 months, investigators at the University of Texas MD Anderson Cancer Center in Houston reported this week at the 49th annual meeting of the American Society of Hematology underway in Atlanta, Georgia.

The phase I/II trial involved 66 patients with acute myeloid leukemia, chronic myeloid leukemia, or myelodysplastic syndrome. Among them, 53 had active disease, and 13 were in remission. Patients were immunized with a vaccine consisting of two peptides derived from the myeloid leukemia-associated antigens, proteinase 3 and neutrophil elastase.

The vaccine "stimulates the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing proteinase 3, resulting in tumor cell lysis," according to the National Cancer Institute.

The first 54 patients received three vaccinations and the last 12 received six vaccinations, all given three weeks apart. Three dosages were tested.

PR1-specific immune response was observed in 25 of the 53 patients with active disease, or 47%. There were clinical responses in nine of those 25, or 36%, compared with three of 28 patients, or 10%, with no immune response.

As noted, the vaccine-induced immune response was associated with a longer event-free survival, at 8.7 months compared with 2.4 months, and a trend toward longer overall survival.

Among the 13 patients in complete remission at baseline, four have remained in remission for a median of 30.5 months, with a range of 11-59 months. Vaccine-specific immune response has lasted for up to four years in some patients.

"A low bone marrow blast count is a significant predictor of an immune response and a longer event-free survival," lead investigator Dr. Muzaffar Qazilbash told Reuters Health. "Patients with an immune response also showed a clinical response and longer overall survival."

"The vaccine augments the immune system, rather than targeting the leukemia cells specifically," he said. "We have seen some relapses in these patients, but fewer than expected and fewer than in those without a clinical response [on immunization]."

"The residual leukemia cells disappear over time in the responders and we cannot detect them after a time," Dr. Qazilbash said. "The molecular markers of leukemia disappear."

"The best time to use the vaccine [at this point] is after first-line treatment failure...We don't see this used as first-line treatment," he said.

Phase III trials with the peptide vaccine are already ongoing.