In order to improve remission rates without causing undue toxicity, we treated 50 patients with relapsed/refractory multiple myeloma according to an institutional sequential treatment algorithm. Bortezomib was given as monotherapy (1.3 mg/m(2) on day 1 + 4 + 8 + 11) followed by the addition of dexamethasone in a first (40 mg on day 1 + 4 + 8 + 11) and bendamustine (50 - 100 mg/m(2) on day 1 + 8) in a second escalation step for patients with less than a minor response. Bortezomib monotherapy was sufficient in 23 (46%) patients, treatment escalation with dexamethasone was necessary in 20 (40%) patients and 7 (14%) patients needed triple combination therapy. Overall response rate was 84% while toxicity was manageable. Median time to progression and overall survival were 8 and 20 months, respectively. In conclusion, this treatment algorithm resulted in responses in the majority of heavily pre-treated patients while at the same time restricting the toxicity of triple combination therapy to only 14% of non-responding patients.