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Fatigue is commonly associated with cumulative effect; although not generally severe, it can be bothersome for some patients, and can be minimized by supportive measures including moderate level of activity, proper fluid intake, and consistent sleeping schedule. In the lenalidomide maintenance studies, around 12%�C27% of patients needed to discontinue therapy due to adverse events.27�C29 Patients who discontinue for reasons other than progressive disease do poorly and hence optimal management of toxicities and dose modification strategies are crucial. Lenalidomide is buy Cyclopamine mainly eliminated unchanged via the kidneys, and renal impairment reduces clearance of lenalidomide. As a result, lenalidomide dose adjustments are needed in patients with renal impairment to avoid excessive and potentially toxic levels of the drug. Lenalidomide is associated with risk of teratogenesis. Pregnancy must be ruled out before starting treatment in women of child-bearing age, and these women must use effective contraception while on lenalidomide. Lenalidomide is approved for marketing in the United States only under a FDA-approved restricted distribution program called Revlimid risk evaluation and mitigation strategy (REMS). As a requirement of the REMS program, access to this medication is restricted. Prescribers and pharmacies must be certified with the program to Mdm2 prescribe or dispense lenalidomide and patients must comply with the program requirements. Lenalidomide has been linked to second primary malignancies in MM. In trials of lenalidomide maintenance, there was a 7%�C8% rate of second primary cancers in the lenalidomide groups compared with 3%�C4% in the placebo groups.27�C29 This increase in second cancers led to discontinuation of lenalidomide in the trial reported by Attal et al.27 In a meta-analysis including seven trials, the 5-year cumulative incidence of secondary primary hematologic malignancies http://www.selleckchem.com/products/sotrastaurin-aeb071.html was higher in patients treated with lenalidomide than in those who were not (3.1% versus 1.4%; HR 3.8; P=0.029).34 In addition, the risk was significantly higher in patients treated with lenalidomide plus oral melphalan than in those treated with melphalan alone (HR 4.86; P