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Introduction.Since publication of the pivotal CLL011 phase 3 trial, combination of chlorambucil and anti-CD20 MAb has become the standard first-line CLL treatment for patients unfit for FCR. Lenalidomide (Len) has been proven effective both as monotherapy and in combination with rituximab. Although recent studies in CLL suggest that Len is mostly beneficial as consolidation treatment, the exact place and duration of this drug is still not optimized. Moreover, Len has shown a distinct and more difficult to manage toxicity profile in the context of CLL, potentially hampering combination treatment with this drug. We therefore conducted a phase 2 study to evaluate efficacy and safety of a combination of chlorambucil, rituximab and individual dosed Len (induction-I) followed by 6 months of Len monotherapy (induction-II).