In this issue of Blood, Jakubowiak and colleagues report outstanding results from a phase 1/2 study using carfilzomib-a next-generation proteasome inhibitor that selectively and irreversibly binds to the proteasome, targeting chymotrypsin-like activity-in combination with lenalidomide and low-dose dexamethasone in newly diagnosed multiple myeloma patients. The study shows excellent response rates, deep and durable responses, continued responses during treatment, and limited severe toxicities.(1)