Jean-luc Harousseau, MD

Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.