Preclinical and clinical studies have demonstrated synergy between bortezomib and pegylated liposomal doxorubicin (PLD) for relapsed/refractory (R/R) multiple myeloma (MM) patients compared to bortezomib as a single agent. This retrospective study evaluated the efficacy and safety of a more frequent low-dose schedule of PLD, bortezomib, and intravenous dexamethasone (DVD) for patients with R/R MM, many of whom were previously treated with bortezomib. Twenty-eight patients with R/R MM were treated, and 23 (83%) had been previously treated with ≥ 1 bortezomib-containing regimen. Treatment consisted of dexamethasone 40 mg intravenously, bortezomib 1.0 mg/m(2), and PLD 5.0 mg/m(2) on days 1, 4, 8, and 11 of a 28-day cycle for a maximum of eight cycles. Patients ranged from 33 to 81 years of age (median, 67) and had received 1-14 prior therapies (median, 5). At baseline, ten, nine, and nine patients were in stages I, II, and III, respectively, as defined by the International Staging System, and eight (29%) patients had elevated serum creatinine levels. The overall response rate was 61%, which included one (4%) complete response, three (11%) very good partial responses, eight (29%) partial responses, and five (18%) minimal responses. Of the 23 patients who had previously received bortezomib, 12 (52%) responded. The regimen was well tolerated with only six patients (21%) who showed worsening of their baseline peripheral neuropathy (PN). One patient discontinued this regimen due to an adverse event (grade II PN). DVD appears to represent a well-tolerated regimen with a high response rate for the treatment of R/R MM patients.