PHILADELPHIA—Several novel biological agents active against multiple myeloma have recently moved from the laboratory to clinical trials. These agents work by targeting the interaction of the tumor cell and its bone marrow microenvironment, offering the potential for more specific, less toxic treatment, compared with conventional chemotherapy.
Paul Richardson, MD, instructor in medicine, Harvard Medical School, and clinical director of the Jerome Lipper Medical Center, Dana-Farber Cancer Institute, presented preliminary clinical data for two new biological agents at a symposium sponsored by the University of Pennsylvania and the Multiple Myeloma Research Foundation.
Thalidomide Analogues
Novel thalidomide(Drug information on thalidomide) analogues are designed to duplicate that agent’s multiple mechanisms of antitumor activity, with higher potency and reduced toxicity. Two classes of thalidomide analogues, known as SelCIDs (selective cytokine-inhibitory drugs) and IMiDs (true immunomodula-tory drugs), are under investigation.
Both drug classes have similar cyto-kine-inhibitory effects, but the IMiDs also stimulate T-lymphocyte production. Phase I studies in multiple myeloma of one IMiD, CC5013 (Revamid, Celgene Corporation), have recently been completed, and phase II studies are now underway.
Typical of agents in its class, CC5013 is up to 2,000 times as potent as thalidomide in vitro and thus can be given at lower doses. The phase I study at Dana-Farber, which was led by Dr. Richardson, followed a typical phase I dose-escalating design (5, 10, 25, and 50 mg/d), with treatment for 28 days to identify the maximum tolerated dose and any antitumor activity, followed by a 1-year extension phase in patients who were benefiting from and tolerating the drug.
Study subjects had relapsed or refractory multiple myeloma. The 25 patients enrolled and treated had a median of three prior treatments, including stem cell transplant and thalidomide in nearly two thirds.
