PR1 peptide vaccination for patients with myeloid leukemias

Abstract

7017 Background: PR1 is a nanomeric HLA-A2-restricted peptide derived from the myeloid leukemia-associated antigens proteinase 3 and neutrophil elastase. Methods: Sixty-six HLA-A2+ patients with acute myeloid leukemia (42), chronic myeloid leukemia (13) or myelodysplastic syndrome (11) were treated with PR1 peptide vaccine. The first 54 patient received three vaccinations, and the last 12 patients were given six vaccinations. The vaccine was injected subcutaneously, at 3 week intervals at one of three dose levels: 0.25, 0.5 or 1.0 mg per vaccination. Immune response to the vaccine was defined as a ≥ 2-fold increase in PR1-specific cytotoxic T lymphocytes. Results: Fifty-three patients had measurable disease (MD) and 13 were in complete remission. The vaccine was well tolerated, with toxicity limited to grade I and II injection site reactions. Forty-four of the 53 patients with MD were evaluable for both immune and clinical responses. PR1-specific immune response was observed in 35/44 (57%) of the evaluable patients. Clinical responses were observed in 10 of the 25 immune responders versus 2 of the 19 immune non-responders (p=0.04). PR1 vaccine-induced immune response was associated with a longer event-free survival, 8.7 months vs. 4.1 months in immune non-responders (p = 0.17). Older age and high blast count were associated with short event-free survival (p=0.01 and <0.001). Conclusion: PR1 peptide vaccine-induced immune response is associated with a superior overall clinical response and a trend towards longer event-free survival in patients with persistent myeloid leukemia. [Table: see text]