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CyBorD is one of the most effective triplet regimens for both transplant-eligible and ineligible patients with multiple myeloma. In comparison, once-weekly bortezomib induction therapy with a reduced dosage of dexamethasone (modified-CyBorD) showed less toxicity but an equally high response rate. However, this modification still resulted in bortezomib-induced PN in more than half of patients. We therefore introduced a once-weekly schedule of bortezomib combined with continuous low-dose oral cyclophosphamide and reduced dosage of dexamethasone (reduced-CyBorD) in transplantineligible patients with multiple myeloma in our hospital. A total of 32 patients, including 20 who were newly diagnosed and 12 who were refractory/resistant, were treated with reduced-CyBorD, and the regimen’s efficacy and safety were evaluated. The median age was 72 years; 17 patients were male and 15 were female. The overall response rate was 90.6% with 43.8% complete response/near complete response. The median progression-free and overall survival was 14.9 months and 43 months, respectively. Three patients (9.4%) developed grade 1 peripheral neuropathy, and no patients had to reduce or discontinue bortezomib. In conclusion, our results suggested that this reduced combination therapy might be a safe and effective approach in transplant-ineligible patients with multiple myeloma.