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Randomized phase II study of proteinase 3-derived PR1 vaccine and GM-CSF with or without peg-interferon alfa-2b to eradicate minimal residual disease in chronic myeloid leukemia

Source: American Society of Clinical Oncology (ASCO)
By: A. Quintas-Cardama, H. M. Kantarjian, E. Wieder, J. Molldrem, J. E. Cortes
05.20.2008

Sub-category: Molecular Targets
Category: Tumor Biology and Human Genetics
Meeting: 2008 ASCO Annual Meeting

Abstract No: 22043
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 22043)
Author(s): A. Quintas-Cardama, H. M. Kantarjian, E. Wieder, J. Molldrem, J. E. Cortes

Background: Imatinib (IM) induces complete molecular responses in a minority of patients (pts) with chronic myeloid leukemia (CML). CML is responsive to T-cell-mediated immunity. The PR1 peptide (VLQELNVTV) is a leukemia-associated antigen presented on HLA-A2 to cytotoxic T lymphocytes (CTL) that preferentially kills leukemia progenitors. Methods: We evaluated the activity of PR1 vaccine (2 mg) with GM-CSF (0.6 mg) and Montanide ISA-51 given subcutaneously to pts with CML on IM in complete cytogenetic response with stable residual molecular disease. Pts were randomized to receive pegylated interferon alfa (PEG-IFN-α; 0.5 µg/kg) with each vaccination. PR1 was administered on weeks 0, 3, 6, and 18. Immune responses were assessed by PR1/HLA-A2 tetramer staining and molecular responses by quantitative PCR in peripheral blood before study entry, prior to each vaccination, and every 3 months thereafter. Results: 4 of the 20 planned HLA-A2+ pts have been accrued. Pt 1 (on IM 600 mg/d for 85 months) and 2 (on IM 800 mg/d for 72 months) received PR1 vaccine+PEG-IFN-α and Pts 3 and 4 (both on IM 400 mg/d, for 43 and 37 months, respectively) received PR1 vaccine alone. BCR- ABL1/ABL1 ratios prior to vaccination were 0.99, 0.79, 0.52, and 0.10, respectively. The median follow-up is 8.5 months (range, 4-11). All pts had mild elevations of BCR-ABL1 transcripts after the first vaccine, followed by steady decline in transcript levels in Pt 1 (>1- log), Pt 2 (<1-log) and Pt 3 (<1-log). Toxicity was limited to grade 1-2 injection site reactions except for Pt 2, in whom PEG-IFN-α was discontinued after 4 mos due to behavioral changes. Immune responses were elicited in Pts 1 (PR1 vaccine+PEG-IFN-α), and 3 (PR1 vaccine). Data on differentiation phenotype, T cell receptor (TCR-alpha-beta) gene usage, TCR avidity, and peptide-induced CTL cytokine secretion profile of PR1-CTLs compared to overall CTL population and CTL with specificity for the HLA-A2-restricted NLV peptide from CMV at each time point after PR1 will be presented. Conclusions: PR1 vaccine in pts with CML in CCyR with stable or rising levels of BCR-ABL1 transcripts on IM induces specific immune responses and ongoing improvement of molecular response.

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