Patients with relapsed multiple myeloma (rMM) often receive multiple lines of therapy, which can make identification of the true efficacy of new agents in clinical trials challenging. Now, a subgroup analysis of data from the ENDEAVOR study reveal that the protesome inhibitor carfilzomib has superior efficacy to that of bortezomib (both in the presence of dexamethasone), regardless of the number of lines of prior treatment, or prior exposure to lenalidomide. Treatment with carfilzomib also resulted in a higher response rate than treatment with bortezomib, again regardless of the type or extent of pretreatment, with similar toxicity profiles observed. These data indicate that carfilzomib is superior to bortezomib in patients with rMM. The findings of these subgroup analyses further support the results of the ENDEAVOR study.