title: Thalidomide and lenalidomide as new therapeutics for the treatment of chronic lymphocytic leukemia.
abstract: The use of nucleoside analog-based chemo-immunotherapeutic regimens over the last decade has significantly improved outcomes in patients with chronic lymphocytic leukemia (CLL). Nonetheless, virtually all patients with CLL relapse from chemoimmmunotherapy and current available therapies are not curative. Identifying therapies that effectively eliminate CLL cells and lack immunesuppression represent an exciting new therapeutic approach. IMiDs are a class of immunomodulating drugs that increase T-cell and NK-cell directed killing of tumor cells. The first generation molecule is thalidomide followed by a second generation molecule lenalidomide that lacks neurotoxicity and is being explored more extensively in clinical trials. Lenalidomide has been shown to benefit patients with multiple myeloma, myelodysplastic syndromes, and lymphoma. Initial reports in patients with relapsed and refractory CLL have shown promising responses. In a subset of patients with CLL complete responses have been noted. Subsequent studies, however, have suggested that this class of drug can also have serious and potentially life-threatening side effects including myelosuppression, tumor flare reaction and in a small subset of patients tumor lysis syndrome. Tumor flare with both thalidomide and lenalidomide appear to be disease specific to CLL and may reflect clinical manifestation of CLL tumor cell activation. As a consequence of these disease specific effects, the optimal safe dose of lenalidomide in CLL remains to be determined but appears to be lower than that tolerated in other B-cell malignancies. To date, biomarkers for response remain poorly defined and the relationship of clinical benefit to tumor flare is uncertain. This review examines the existing literature on the use of IMiDs in patients with CLL and provides suggestions for future research in this area.
authors.affiliation: Division of Hematology Oncology, Department of Medicine, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Awan
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Johnson
authors.forename: Rosa
authors.initials: R
authors.lastname: Lapalombella
authors.forename: Weihong
authors.initials: W
authors.lastname: Hu
authors.forename: Margaret
authors.initials: M
authors.lastname: Lucas
authors.forename: Beth
authors.initials: B
authors.lastname: Fischer
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002986:Clinical Trials as Topic; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008495:Medical Oncology / Q000379:methods*; D013601:T-Lymphocytes / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D013792:Thalidomide; D000077269:Lenalidomide