In an effort to maintain high primary response rates against multiple myeloma and without serious toxicity, we assessed 3 different bortezomib combinations in small numbers of patients, with combinations that included cyclophosphamide and lenalidomide in modest doses and for short courses. Remissions occurred in approximately 90% of patients, with rare episodes of serious drug-related adverse effects.Recent bortezomib combinations have induced remission in approximately 90% of patients newly diagnosed, with moderate frequency of adverse effects.In an attempt to reduce adverse effects, and to prepare qualified patients for early intensification, we assessed the antimyeloma effect and toxicity of 3 different bortezomib combinations in small numbers of patients.With reduced doses and short durations of exposure, we combined bortezomib with (a) cyclophosphamide/dexamethasone, (b) lenalidomide/dexamethasone/liposomal doxorubicin, and (c) cyclophosphamide/dexamethasone/lenalidomide.Response rates were high, with rare episodes of severe drug-related toxicity.Further study of similar combinations of effective drugs given in limited doses and for short durations would be useful.