Laboratory studies evaluating the activity of
Celgene’s immunomodulatory drugs (IMiDs) on multiple myeloma cells suggest that these agents may be beneficial in the treatment
of multiple myeloma. Researchers from the Dana-Farber Cancer Institute and
Harvard Medical School presented data on the IMiDs at the 42nd annual meeting of
the American Society of Hematology.
The data demonstrate a dose-dependent effect of IMiDs on
multiple myeloma cells and show their impact at the molecular level on multiple
myeloma cell growth. In addition, the IMiDs were found to have direct antitumor
effects, including enhancement of multiple myeloma cell death (apoptosis) and
cell-cycle arrest. These compounds were also synergistic with other antimyeloma
agents in some of the cell lines studied.
"These results support previously reported data and
demonstrate growing evidence for direct activity of the IMiDs against human
multiple myeloma cells," said Kenneth C. Anderson, MD, professor of
medicine in the department of adult oncology at the Dana-Farber Cancer Institute
and Harvard Medical School. "The results from these studies provide the
framework for a new biologically based treatment paradigm, using these agents
either alone or in combination with conventional therapies, to achieve improved
outcome in this disease."
The IMiDs are structural analogs of thalidomide that have
significantly greater immunomodulatory activity in vitro but do not demonstrate
teratogenicity in animal models. In addition, in a phase I healthy human
volunteer trial, they did not produce the sedative effect associated with
thalidomide. These compounds have been reported to enhance T-cell proliferation
and interleukin (IL)-2 production. The IMiDs have also been shown to be potent
inhibitors of inflammatory cytokines (eg, tumor necrosis factor-alpha and
IL-1-beta), while stimulating the anti-inflammatory cytokine IL-10.
According to David I. Stirling, PhD, chief scientific officer of
Celgene Corporation and one of the researchers involved in these studies,
"these findings support our basic understanding of the biological activity
of these compounds as well as the scientific rationale for initiating phase I/II
clinical development with our lead IMiD in myeloma patients." The lead
compound, currently in clinical trials in myeloma patients, was selected based
on the overall activity demonstrated in these and other test systems, as well as
on the toxicologic and pharmacologic properties of the compounds.