Cytogen: Early data shows Quadramet/Velcade combination effective in myeloma-infected mice

By E. Janene Geiss

Philadelphia, Dec. 12 - Cytogen Corp. announced Monday that preclinical data on its flagship product Quadramet (samarium Sm-153 lexidronam) in combination with Millennium Pharmaceuticals, Inc.'s Velcade (bortezomib) demonstrated broad anti-cancer activity in a mouse myeloma model.

Results included greatly prolonged median survival, rapidly reduced clonogenicity of bone-marrow resident 5TGM1 cells, slowed elevation of serum myeloma-associated paraprotein levels and longer term preservation of bone mineral density, according to a company news release.

Data from the new study was presented by researchers from the Mayo Clinic College of Medicine at the American Society of Hematology annual meeting.

In vitro studies demonstrated synergistic killing of myeloma cell lines with the combination of Quadramet and bortezomib, officials said.

In vivo studies demonstrated that the combination therapy greatly prolonged median survival of mice and was well-tolerated. The preclinical study was conducted in mice injected with myeloma 5TGM1 cells.

This mouse myeloma model exhibits changes in the skeleton that are reported to be indistinguishable from those seen in human patients and is used for studies of pathogenetic mechanisms in myeloma and for preclinical evaluation of novel anti-tumor strategies, officials said.

Using the 5TGM1 myeloma model, the median survivals of mice treated with saline, two doses of bortezomib or a single non-myeloablative dose of Quadramet were 21, 22 and 28 days respectively.

In contrast, mice treated with combination therapy comprising two doses of bortezomib one day prior to and one day following Quadramet showed a greatly prolonged median survival of 49 days, officials said.

The authors said they concluded that bortezomib is a potent in vivo radiosensitizer that greatly enhances the therapeutic potency of Quadramet in the syngeneic, orthotopic 5TGM1 myeloma model without increasing myelotoxicity.

Cytogen has already initiated phase 1 clinical trials to evaluate treatment involving a combination of Quadramet plus bortezomib in patients with relapsed or treatment-refractory multiple myeloma.

Quadramet also is currently being evaluated in multiple myeloma patients in a phase 1 combination trial with Novartis' Zometa (zoledronic acid), officials said.

Cytogen is a Princeton, N.J., biopharmaceutical company that acquires, develops and commercializes innovative molecules targeting the sites and stages of cancer progression.

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