Vaccine improves event-free survival for leukemia patients

December 09, 2007

ATLANTA - Patients whose immune system responded to a peptide vaccine for leukemia enjoyed a median remission that was more than three times longer than non-responders, a team led by researchers at The University of Texas M. D. Anderson Cancer Center reports at the 49th Annual Meeting of the American Society of Hematology.

Immune response to the PR1 vaccine was associated with an 8.7 month event-free survival compared with 2.4 months for non-responders. Clinical responses ranging from improvements in blood counts to complete cytogenetic remission were observed in 36 percent of the responders compared with 10 percent of non-responders.

"We did not expect dramatic responses in this clinical trial, and were pleasantly surprised to see the clinical responses and improved event-free survival" says Muzaffar Qazilbash, M.D., associate professor in M. D. Anderson's Department of Stem Cell Transplantation and Cellular Therapy.

The Phase I/II clinical trial that ran from 2000 to 2006 was designed to assess the vaccine's safety and its ability to elicit an immune response. Toxicity was limited to low-grade injection site side effects such as redness, swelling and some pain.

The PR1 vaccine is derived from two myeloid leukemia-associated antigens, proteins that are either overexpressed or aberrantly expressed in cancer cells. When PR1 elicits an immune response, PR1-specific cytotoxic T lymphocytes are produced that selectively kill three types of leukemia - myelodysplastic syndrome, acute myelogenous leukemia and chronic myelogenous leukemia.

Out of 66 patients in the trial, 53 had active disease and 13 were in remission when they entered the trial. Of the 53 with one of the three types of active leukemia, 25 (47 percent) had an immune response and 28 did not. Nine out of 25 responders (36 percent) had some type of clinical response compared with three of the 28 non-responders (10 percent).

Among the 13 in remission at the start of the trial, four remained in remission for a median time of 30.5 months.

In phase I trials, patients have been heavily pretreated with other therapies. "We had good accrual and a reasonably long follow-up of almost three years," Qazilbash says, "For a Phase I/II, that's a fair number of patients."

"Immunotherapy works best for low level of disease," Qazilbash says. "So patients with low leukemia burden may get the maximum benefit."
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Disease-specific Phase II clinical trials of the vaccine for chronic myelogenous leukemia and myelodysplastic syndrome are planned or under way at M. D. Anderson. The Vaccine Company, which makes the PR1 vaccine, is conducting a national Phase III clinical trial for acute myelogenous leukemia.

To be eligible for PR1, patients must be positive for a specific major histocompatibility molecule, HLA-A2. The molecule presents antigens so they can be "seen" by T lymphocytes. Qazilbash says about 40 percent of the general population is HLA-A2+.

The PRI vaccine was developed by Jeffrey Molldrem, M.D., professor in M. D. Anderson's Department of Stem Cell Transplantation. Molldrem co-founded The Vaccine Company in 2003 and the company licensed the technology from M. D. Anderson in 2004. M. D. Anderson has an equity interest in the Vaccine Company. These arrangements are managed in accordance with M. D. Anderson's conflict of interest policies.

Co-authors with Qazilbash and Molldrem are Eric D. Weider, Ph.D., Rosa L. Rios, Sijie Lu, Ph.D., Shreya Kant, Sergio Giralt, M.D., Krishna Komanduri, M.D., and Richard Champlin, M.D., all of the Department of Stem Cell Transplantation and Cellular Therapy; Peter F. Thall, Ph.D., and Xuemei Wang, of M. D. Anderson's Department of Biostatistics; and Elihu H. Estey, M.D., of Jorge Cortes, M.D., M. D. Anderson's Department of Leukemia.

University of Texas M. D. Anderson Cancer Center

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