PHILADELPHIASeveral 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.
Novel 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
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.