Vorinostat plus bortezomib for the treatment of relapsed/refractory multiple myeloma: A case series illustrating utility in clinical practice

Introduction: Increasing numbers of patients are presenting with relapsed/refractory multiple myeloma (MM) following treatment with bortezomib. Therefore, there is a need for effective and well-tolerated treatment strategies after failure of bortezomib-based regimens. Vorinostat, a histone deacetylase inhibitor, has demonstrated antiproliferative and proapoptotic activity alone and in combination with bortezomib in preclinical models of MM. Preliminary results from ongoing phase I trials have demonstrated the clinical activity of vorinostat in combination with bortezomib in patients with MM. This case series reports our experience of combined vorinostat and bortezomib in 6 patients with relapsed/refractory MM after previous bortezomib. Materials and Methods: Patients received oral vorinostat 300 mg or 400 mg once daily (days 1-14) and bortezomib 1.3 mg/m² on days 1, 4, 8, and 11 in a 21-day cycle. Results: All patients derived clinical benefit from combined vorinostat and bortezomib, with objective response observed in 5 of the 6 patients (≥minimal response), including 1 very good partial response;stable disease was observed in the remaining patient. Patients remained on therapy until disease progression. Combined vorinostat and bortezomib therapy was well tolerated: grade 2 nausea and diarrhea were the only adverse events reported. No patients discontinued therapy because of toxicity, and no dose adjustments were required for either agent. Conclusion: These results suggest that combined vorinostat and bortezomib therapy is effective in patients with relapsed/refractory MM after failure of previous bortezomib-based regimens and support further evaluation of this combination in randomized trials.