Clinical trials of the combination of cyclophosphamide, bortezomib, and steroids in relapsed/refractory myeloma have shown promising results, but there is little information about real-world outcomes. We retrospectively reviewed the results of weekly CyBorP(D) in 96 patients treated off-study. The overall response rate was 69%; median progression-free survival was 16.2 months. Toxicity was mild with low rates of myelosuppression and neuropathy. Introduction: Cyclophosphamide, bortezomib, and prednisone (CyBorP) is a highly effective, well-tolerated regimen in relapsed/refractory multiple myeloma. CyBorP, originally developed at our center to include weekly bortezomib (Bor) and alternate-day prednisone (P), was recently modified so that weekly dexamethasone (D) replaced prednisone. Patients and Methods: To assess the effectiveness and tolerability of CyBorP/D in real-world practice, we identified 96 relapsed/refractory patients who received >= 1 28-day cycle of CyBorP/D, consisting of cyclophosphamide 300 mg/m(2) (days 1, 8, 15, and 22), Bor 1.0 to 1.5 mg/m(2) (days 1, 8, and 15), and either P 50 to 100 mg on alternate days or D 20 to 40 mg weekly between 2007 and 2013. Results: Sixty-six (69%) patients achieved >= partial response: 16 with clinical complete response and 25 with very good partial response; 22 others had stable disease. Progression-free and overall survival for all patients were 16.2 months (95% confidence interval [CI], 7.7-20.1 months) and 26.3 months (95% CI, 21.6-81.2 months), respectively. Although 26 patients had prior Bor exposure, there was no difference in progression-free or overall survival versus Bor-naive patients. Conclusion: Toxicities with CyBorP/D were generally mild and manageable. New onset peripheral neuropathy was seen in 13 cases; 9 of 26 patients with pre-existing peripheral neuropathy developed worsening symptoms. No second primary malignancies were observed. (C) 2016 Elsevier Inc. All rights reserved.