We conducted a single-center, prospective clinical trial in which a subcutaneous bortezomib (Bor) regimen [1.6 mg/m2 per month (BD 1.6 mg/m2 therapy)] was administered to 22 multiple myeloma patients. All patients had been treated sufficiently with once-monthly subcutaneous Bor injections (BD 1.3 mg/m2therapy). Of the 22 patients, 13 had IgG-, 2 had IgA-, and 7 had Bence-Jones protein (BJP)-type multiple myeloma. The observation period for therapeutic effect determination ranged from 84 to 412 days (median: 400 days). Therapeutic effects were investigated in 15 patients during the increase in Bor from 1.3 to 1.6 mg/m2, and none achieved complete remission (CR), very good partial remission (VGPR), or partial remission (PR). Given the small number of patients, a significant conclusion must be reached carefully. However, the chance of stronger success with increases in Bor is low for patients who have already undergone long-term 1.3 mg/m2 Bor treatment. Furthermore, non-hematological toxicity was seen in 12 of 22 patients, so increasing Bor to 1.6 mg/m2 should be considered carefully. However, the statuses of patients in this study suggest that once-monthly Bor could inhibit disease progression. In future we should investigate low-frequency Bor maintenance therapy.