Thalidomide in newly diagnosed multiple myeloma and overview of experience in smoldering/indolent disease

Based on the activity of single-agent thalidomide demonstrated in relapsed or refractory multiple myeloma, investigators have evaluated the role of this agent in the treatment of earlier stage disease. Two key phase II trials of thalidomide plus dexamethasone in patients with previously untreated symptomatic multiple myeloma have yielded overall response rates of 64% to 73%. Comparable response rates, reduced toxicity, and increased patient convenience with oral administration suggest it may offer an alternative to standard infusional chemotherapies, such as vincristine/doxorubicin/dexamethasone (VAD), before stem cell mobilization and high-dose chemotherapy in patients with active disease; further study is warranted. Two key phase II trials of single-agent thalidomide in patients with smoldering/indolent (asymptomatic) disease have yielded overall response rates of approximately 35%, and further study of thalidomide in this setting is also indicated. The primary toxicities of thalidomide-based therapy are neuropathy, sedation/fatigue, constipation, and rash. Studies of thalidomide in combination with dexamethasone suggest toxicities of both agents may be increased due to the synergy of these agents. Phase III trials of thalidomide in newly diagnosed symptomatic multiple myeloma or smoldering/indolent disease are ongoing.