High-Dose Therapy in Amyloidosis

Abstract

High-dose melphalan with autologous stem cell support (SCT) has improved outcomes for patients with systemic AL amyloidosis. A significantly greater proportion of patients remain alive and progression-free 5 or 10 years post-therapy than with historical traditional regimens. However, at most only one-third of newly diagnosed AL patients are eligible for SCT and, as attempts to minimize morbidity and mortality lead to refined patient selection, fewer AL patients may ultimately have SCT made available to them. Standard oral melphalan and dexamethasone, as well as combinations that include the novel agents lenalidomide and bortezomib, may allow for rapid elimination of circulating light chains and achieve response rates similar to SCT. In addition, as more data are obtained about complete response frequency, response duration, and tolerability of the novel agents in AL patients, it is possible that the risk-to-benefit ratio of high-dose therapy as initial treatment will become less favorable and that SCT may become more appropriate as second-line therapy. Indeed, the central challenge of the upcoming decade will be how and when to best incorporate the novel agents, either alone or in combination with both conventional and high-dose chemotherapeutic regimens, into our armamentarium against AL. Certainly, more randomized clinical trials will be needed to answer these questions, requiring cooperative group involvement and cooperation among amyloidosis treatment centers. Fortunately, risk-adapted high-dose therapy and the novel agents have greatly expanded the options for AL patients compared with a decade ago and the future continues to look bright.