Multiple myeloma remains incurable despite the use of novel agents. Dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) is one of the salvage options, but there has been a lack of data on salvage DCEP in patients with previous exposure to novel agents. A total of 59 patients who received DCEP chemotherapy between 2006 and 2013 were retrospectively reviewed. The patients who had been exposed to thalidomide, lenalidomide, or bortezomib prior to DCEP were eligible. The median age at DCEP was 58 years, and DCEP treatment was initiated at a median of 34.9 months from diagnosis. Before DCEP, patients exposed to a median of three lines of treatment and 55 patients (81.4 %) had undergone autohematopoietic stem cell transplantation. Among 51 patients with data available for response assessment, response rate was 45.1 % (1 with complete response, 1 with very good partial response, and 21 with partial response); an additional 18 patients benefited from this regimen (8 with minor response and 10 stable diseases). Grade ≥3 neutropenia was observed in 91.5 %. Treatment-related mortality (TRM) was reported in eight patients (14.8 %), and seven of eight deaths were related to febrile neutropenia. Median overall survival and progression-free survival were estimated at 8.0 and 3.7 months, respectively. DCEP is an effective salvage treatment options for relapsed or refractory multiple myeloma in the setting of previous use of novel agents. However, hematologic toxicities and TRM were substantial, and concurrent use of prophylactic granulocyte-colony stimulating factor is warranted.