title: A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma.
abstract: Lenalidomide is an oral non-chemotherapy immunomodulator with direct and indirect effects on non-Hodgkin lymphoma (NHL) cells and with single-agent activity in relapsed/refractory aggressive and indolent B-cell NHL, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, and follicular lymphoma. Based on the pivotal phase II MCL-001 trial of lenalidomide in heavily pretreated patients with relapsed/refractory MCL, lenalidomide was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL after failure of two prior therapies, one of which includes bortezomib, at a recommended starting dose of 25 mg on days 1-21 of each 28-day cycle. Lenalidomide enhanced the survival benefit in combination with rituximab in preclinical models, prompting clinical evaluation of the lenalidomide-rituximab (R2) combination. In phase II trials, lenalidomide 20 mg on days 1-21 in combination with different standard-dose rituximab schedules exhibited promising activity in both first-line and relapsed/refractory disease across multiple B-cell NHL subtypes. The feasibility of combining lenalidomide with immunochemotherapy, including R-CHOP and rituximab-bendamustine, has been demonstrated in phase I/II trials. These latter regimens are currently being evaluated in ongoing phase II and III trials. The role of lenalidomide monotherapy and R2 in maintenance therapy is also being examined. Based on available evidence, a comprehensive review of lenalidomide in all treatment phases of B-cell NHL-relapsed/refractory disease, first-line, and maintenance-is presented here.
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester witzig@mayo.edu.
authors.forename: T E
authors.initials: TE
authors.lastname: Witzig
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester.
authors.forename: G S
authors.initials: GS
authors.lastname: Nowakowski
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester.
authors.forename: T M
authors.initials: TM
authors.lastname: Habermann
authors.affiliation: John Theurer Cancer Center at HUMC, Hackensack.
authors.forename: A
authors.initials: A
authors.lastname: Goy
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Hernandez-Ilizaliturri
authors.affiliation: Department of Hematology, Città della Salute e della Scienza Hospital and University, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiappella
authors.affiliation: Department of Hematology, Città della Salute e della Scienza Hospital and University, Torino, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Vitolo
authors.affiliation: Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: N
authors.initials: N
authors.lastname: Fowler
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Czuczman
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077269:Lenalidomide; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; C571759:R-CHOP protocol; D000069283:Rituximab; D013792:Thalidomide; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D000077269:Lenalidomide; D011241:Prednisone
keywords: diffuse large B-cell lymphoma; follicular lymphoma; lenalidomide; mantle cell lymphoma; non-Hodgkin lymphoma; rituximab