Results of First-in-Man Phage Idiotype Vaccine Study in Patients with Multiple Myeloma.

Idiotypes (Id) expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and may therefore be used as a target for vaccine immunotherapy. In this phase I/II study we have evaluated the feasibility, safety and response of phage idiotype vaccination in patients with relapsed multiple myeloma (MM) using phage displayed Id-specific proteins as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) as immunoadjuvants.

Patients received a total of 6 intradermal/subcutanous (i.d./s.c) immunizations of phage idiotype vaccines at day 1, 7, 14 and at week 4, 8 and 12. The vaccine dose started from 0.25 mg for the first 5 patients and was escalated to 1.25 mg (patient 6-10) and 2.5 mg (patient 11-15) if no dose-limiting toxicity was observed. Each vaccine contained 0.2 mg GM-CSF (Leukomax®) as adjuvant and 0.2 mg KLH (Immucothel®) as control antigen. They received all subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting.

15 patients who had previously been treated with high-dose chemotherapy (HDT) followed by peripheral blood progenitor cell (PBPC) transplantation entered this study. All patients were in a beginning relapse after high dose therapy at the time of vaccination. Patients with fulminant relapse or patients with active infection and hematopoetic insufficiency after HDT were excluded.

The results of this first-in-man phase I/II trial for phage-based idiotype vaccination clearly demonstrated the feasibility, safety and excellent tolerability of the phage vaccination whereas local skin reactions were the most frequent side effects. Furthermore, we were able to gather precious data regarding the immunology of phage vaccines in man. We could confirm our preclinical data, that phages are good immunogens, capable of inducing a strong immune response mainly of IgG1-type and therefore enabling ADCC and CDC immune response. Altogether these data suggest, that phage idiotype vaccines has the potential to exert a beneficial effect especially in patients with minimal residual disease. Strikingly, the immune response of phages compared to the well-known KLH particles showed > 10 time higher antibody titer than KLH, which emphasize the prominent immunogenicity of the phages. Overall these data pinpoint to a promising role of phage vaccination for the immunotherapy of cancer but further studies are necessary to evaluate the full potential of phage vaccines.

Roehnisch:Apalexo Biotechnologie GmbH: Research Funding. Nagel:Apalexo Biotechnologie GmbH: Research Funding. Donceau:Apalexo Biotechnologie GmbH: Research Funding. Bourquin:Apalexo Biotechnologie GmbH: Research Funding.