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WT1 peptide vaccine produces durable disease control in some patients with AML or MDS; a phase II study is on the horizon

WT1 peptide vaccine produces durable disease control in some patients with AML or MDS; a phase II study is on the horizon

ASCO—An HLA-A2-restricted peptide vaccine given as salvage therapy to patients with acute myeloid leukemia or myelodysplastic syndrome showed evidence of immunological, molecular, and clinical efficacy, German investigators reported at ASCO 2007 (abstract 3008).

By week 10 after starting a series of vaccinations, more than half the patients experienced an immunological response, and, for many, these were accompanied by a relapse-free period lasting several months, reported Ann Letsch, MD, of Charite Campus Benjamin Franklin, Universitatsmedizin, Berlin.

The HLA-A2-restricted WT1.126-134 peptide may represent "close to an ideal tumor antigen," Dr. Letsch said. WT1 is an embryonic transcription factor that is highly expressed in AML (driving blast proliferation) and various carcinomas. WT1-specific T cells lyse only AML blasts and not stem cells, and the vaccine has not shown toxicity in animal models.

Her study included 29 patients with WT1-expressing AML or MDS with an IPS score ≥ 1.5 or WTI expression in the peripheral blood. Patients were not candidates for stem cell transplant and had no other reasonable treatment options. All were HLA-A2 positive.

The patients received the WT1 peptide 0.2 mg on day 3, plus GM-CSF 75 µg/d on days 1-4 as a dendritic cell stimulant, and 1 mg KLH on day 3 as a T-helper protein.

The first cohort (n = 13) received the vaccine every 2 weeks for 4 weeks, then every 4 weeks thereafter. The second cohort received the vaccine every 2 weeks for 12 weeks, and every 4 weeks thereafter (n = 16). Patients experiencing disease progression could continue to receive up to six vaccinations if inclusion criteria were still met and chemotherapy was not required.

The cohorts were combined in the final analysis at week 10, which included 26 patients for efficacy, 23 for mRNA WT1 levels, and 25 for T-cell response.

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