Background: Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on NK cells and plasma cells that enhances the activity of lenalidomide and bortezomib in multiple myeloma (MM). We studied elotuzumab with pomalidomide, bortezomib, and dexamethasone (elo-PVD) in relapsed and refractory MM. Methods: The primary objective was to determine the overall response rate (ORR). Patients with refractory disease and ≥1 prior lines of treatment (including lenalidomide and a proteasome inhibitor) were eligible to participate. Elotuzumab was weekly for the first 2 cycles and then every other week. Pomalidomide was on days 1-21; bortezomib was on days 1, 8, 15; and dexamethasone was weekly. Each cycle was 28 days. Results: At time of data cutoff, 33 patients (pts) who started treatment were evaluable. The median age was 64 (range 52-79), and the median number of prior regimens was 3 (range 1-9); 27% had high risk FISH. All pts had prior lenalidomide and proteasome inhibitors (bortezomib 94%, 76% carfilzomib) and were refractory to their last line of therapy. Prior therapies also included: auto SCT (45%), pomalidomide (36%), daratumumab (21%), and isatuximab (3%). 31 pts were assessable for response (2 patients did not complete cycle 1 due to rapid disease progression or stroke and were not evaluable). The median length of follow up was 3.3 months (range 0.5-18.2): 23 pts continue on study; 7 pts discontinued for progressive disease and 3 pts discontinued for adverse events (AEs) (sepsis, pneumonia, or stroke). Best ORR was 52% (PR = 11, VGPR = 4, CR = 1); ORR for pts with prior anti-CD38 antibody, 43%; carfilzomib, 43%; pomalidomide, 40%. Median PFS was 9.7 months (95% CI 7.5-Inf). Grade 3-4 hematologic AEs included anemia (7%), neutropenia (34%), and thrombocytopenia (17%). Common non-hematologic AEs all grades included fatigue (38%), upper respiratory infection (38%), constipation (38%), hyperglycemia (38%), and neuropathy (38%, Gr 1-2 only), with 2 possibly related deaths (sepsis, pneumonia). Conclusions: Elo-PVD shows encouraging responses in patients with refractory MM. Treatment was well-tolerated with manageable toxicity and attention to infectious AEs. Clinical trial information: NCT02718833