Potent Thalidomide Analogs Active Against Multiple Myeloma

BOSTON—Laboratory studies assessing the effect of potent thalidomide analogs on multiple myeloma cells suggest they have potential for the treatment of multiple myeloma, investigators from Dana-Farber Cancer Institute and Harvard Medical School reported.

Among the analogs tested were three immunomodulatory drugs (IMiDs), being developed by Celgene Corporation (Warren, NJ). These agents markedly stimulate T-cell proliferation as well as interleukin-2 (IL-2) and interferon-gamma production.

Kenneth C. Anderson, MD, of Dana-Farber Cancer Institute, reported that all three of the IMiDs tested were found to be dose-dependent inhibitors of multiple myeloma cells from human multiple myeloma cell lines and from myeloma patients (Blood 96:2943-2950, 2000).

The IMiDs were also effective against cell lines resistant to conventional antimyeloma agents, including doxorubicin, mitoxantrone (Novantrone), melphalan (Alkeran), and dexamethasone. Furthermore, combination treatment with dexamethasone and IMiDs significantly improved inhibition of multiple myeloma cell line proliferation.

The studies showed that IMiDs act directly against human multiple myeloma cells by inducing apoptosis or G₁ growth arrest, the researchers said.

“These results provide the framework for the development and testing of a new biologically based treatment paradigm that uses these novel agents, either alone or together with conventional therapies, to target both the tumor cell and its microenvironment, overcome classical drug resistance, and achieve improved outcomes in this presently incurable disease,” the investigators concluded.