Multiple myeloma is the second most common hematologic malignancy. It accounts for 20,580 new cancer cases in the USA in 2009, including 11,680 cases in men, 8,900 cases in women, and 10,580 deaths overall. Although the disease remains still incurable, outcomes have improved substantially over recent years thanks to the use of high-dose therapy and the availability of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib. Various trials have shown the advantages linked to the use of novel agents in the transplant and not-transplant settings. In particular, this paper will present an overview of the results achieved with lenalidomide-containing combinations in patients eligible for high-dose therapies, namely, young patients. The advantages obtained should always be outweighed with the toxicity profile associated with the regimen used. Therefore, here, we will also provide a description of the main adverse events associated with lenalidomide and its combination. 1. Introduction For many years, the combination vincristine-doxorubicin-dexamethasone (VAD) was the standard induction treatment for young patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Ten years ago patients candidate for transplant used to receive VAD for 4–6 cycles before undergoing transplantation, leading to a partial response (PR) rate ranging from 52% to 63%, with 3% to 13% of complete response (CR) rate. The availability of new drugs, such as thalidomide, lenalidomide, and bortezomib, has dramatically changed the treatment paradigm of this disease and significantly increased the therapeutic options [1]. Lenalidomide is an immunomodulatory drug with higher potency than its analogue thalidomide and without sedative or neurotoxic adverse effects. Differences between lenalidomide and thalidomide activity have been shown in preclinical studies. In comparison with thalidomide, lenalidomide has more antiproliferative activity against hematopoietic tumors, including myeloma cell lines and patients’ cells [2, 3], increased inhibition of tumor necrosis factor secretion from activated monocytes, and increased activation of T cells and natural killer cells [4]. In contrast, thalidomide has more antiangiogenic activity than lenalidomide in human models. Both lenalidomide and thalidomide interfere with key events in the angiogenic process, and activities of these drugs can be differentiated qualitatively depending on what component is studied [5]. Lenalidomide is administered orally, and the
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