Thalidomide, lenalidomide and rituximab have no direct effect on MCL cells. However, both indirectly affect peripheral blood mononuclear cell-mediated cytotoxicity, and rituximab induces both complement-dependent and antibody-dependent cellular cytotoxicity (ADCC) against MCL cells. Rituximab-induced ADCC is enhanced by lenalidomide and thalidomide. In a 2004 series, thirteen patients of sixteen enrolled (81%) experienced an objective response, with 5 complete responders (31%). Median progression-free survival (PFS) was 20.4 months (95% confidence interval [CI], 17.3-23.6 months), and estimated 3-year survival was 75%. In patients achieving a complete response, PFS after rituximab plus thalidomide was longer than PFS after the preceding chemotherapy. Severe adverse events included 2 thromboembolic events and 1 grade IV neutropenia associated with thalidomide.Several similar studies show promise, but the combination of rituximab and thalidomide still requires investigation and is not currently recommended by any guidelines.
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