Background Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy. Patients and methods We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib. Results Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1-57), cumulative bortezomib dose was 41.8 mg/m(2) (2.6-67.6) and median dose intensity was 1.0 mg/m(2)/wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77-104) and 209 weeks (95% CI 157-259) respectively. Patients who progressed