Objective To investigate the therapeutic efficacy and adverse reactions of a modified DCEP for relapsed/refractory multiple myeloma (MM). Methods Enrolled in the study were 5 patients suffering from relapsed/refractory MM, who were treated with modified DCEP in the Department of Geriatric Oncology of the First Affiliated Hospital of Chinese PLA General Hospital. Their clinical data were retrieved, including age, gender, peripheral blood and bone marrow characteristics. The patients were treated with a modified DCEP, and its therapeutic efficacy and adverse reactions were evaluated. Results The 5 patients (1 man and 4 women) were aged from 51 to 75 years. All of them were administered with a modified DCEP with a median course of 2 (range from 2 to 5) and a median follow-up of 22 months. Partial remission was observed in 1 patient with progression-free survival of 2 months, minimal response in 1 patient with progression-free survival of 6 months, stable disease in 2 patients, and progression in 1 patient. The main adverse reactions were gastrointestinal symptoms (grade Ⅱ in 4) and fatigue (grade Ⅱ in 3). One patient developed myelosuppression (grade Ⅳ) complicated with pulmonary infection. Conclusion Modified DCEP is effective and well-tolerated in the patients with relapsed/refractory MM.