Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del (17p) and t (4; 14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P< 0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P= 0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del (17p)(4.6 versus 1.1 months; HR, 0.34; P< 0.001), t (4; 14)(2.8 versus 1.9 months; HR, 0.49; P= 0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P< 0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or high-dose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P= 0.008) in patients with del (17p), 7.5 versus 4.9 months (HR, 1.12; P= 0.761) in those with t (4; 14), and 14.0 versus 9.0 months (HR, 0.85; P= 0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del (17p)(31.8% versus 4.3%), whereas it was similar in patients with t (4; 14)(15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del (17p) and/or t (4; 14). This study is registered at ClinicalTrials. gov as