Although multiple myeloma remains incurable outside of allogeneic hematopoietic stem cell transplantation, novel agents made available only in the last few decades have nonetheless tremendously improved the landscape of myeloma treatment. Lenalidomide, of the immunomodulatory class of drugs, is one of those novel agents. In the non-transplant and relapsed/refractory settings, lenalidomide clearly benefits patients in terms of virtually all meaningful outcomes including overall survival. Data supporting the usage of lenalidomide as part of treatment approaches incorporating high-dose chemotherapy with autologous stem cell support (ASCT) are less mature as pertains to such long-term outcomes and toxicity, and lenalidomide is not currently approved by regulatory agencies for use in the context of ASCT in either the United States or Europe. That said, relatively preliminary efficacy data describing lenalidomide as a component of ASCT-based treatment approaches to MM are indeed promising, and consequently lenalidomide’s role in ASCT-based treatment strategies is growing. In this review we summarize existing data that pertains to lenalidomide in the specific context of ASCT, and we share our thoughts on how our own group applies these data to approach this complex issue clinically. 1. Introduction Multiple myeloma (MM) is a malignancy of plasma cells that strikes roughly 20,000 and kills 10,000 US Americans yearly [1]. Outside of allogeneic stem cell transplantation, MM remains incurable, albeit increasingly treatable, thanks to the advent of novel agents including those that are currently approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA)—bortezomib, thalidomide, and lenalidomide. Regarding the latter, the initial phase one study of lenalidomide (Revlimid), then known as CC-5013, first appeared in the scientific literature in 2002 and attention rapidly focused on CC-5013’s activity even in multiply relapsed and refractory MM (RRMM) [2]. That study and others led to the later definitive phase three MM-009 and 010 trials, which showed overall survival benefits for RRMM patients on lenalidomide and dexamethasone in contrast to those on dexamethasone alone [3, 4]. FDA and EMA approval for lenalidomide followed, and lenalidomide and dexamethasone became established as a standard of care for RRMM. Subsequent clinical trials have further explored the role of lenalidomide as a part of treatment strategies for newly diagnosed MM (NDMM) that both include or exclude high-dose therapy with autologous hematopoietic stem
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