title: Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas.
abstract: BACKGROUND
  Lenalidomide is an immunomodulatory drug with effects on the immune system that may enhance antibody-dependent cell-mediated cytotoxicity and reverse tumor-induced immune suppression. Furthermore, single-agent lenalidomide has therapeutic activity in relapsed/refractory B-cell lymphomas. These immunologic effects potentially may enhance the action of rituximab.
  
  
  METHODS
  To test the efficacy of lenalidomide combined with rituximab, the authors conducted a phase 2 trial of lenalidomide, low-dose dexamethasone, and rituximab in patients who had rituximab-resistant, relapsed/refractory, indolent B-cell or mantle cell lymphomas. Patients received two 28-day treatment cycles of lenalidomide 10 mg daily and dexamethasone 8 mg once weekly (part I). During cycle 3, 4 weekly doses of rituximab 375 mg/m2 were administered with lenalidomide-dexamethasone (part II). After the part II response assessment, stable or responding patients continued to receive lenalidomide-dexamethasone.
  
  
  RESULTS
  Twenty-seven patients with follicular (n=18), mantle cell (n=5), small lymphocytic (n=3), and marginal zone (n=1) lymphomas started therapy; 3 of 27 patients discontinued therapy because of adverse events and were not evaluable for response. For 24 patients, the overall response rate after part I was 29% (4 patients had a complete response [CR] or CR unconfirmed, and 3 patients had a partial response), and the overall response rate after part II was 58% (8 patients had a CR, and 6 patients had a partial response). For 27 patients, at a median follow-up of 12.2 months, the median progression-free survival was 23.7 months.
  
  
  CONCLUSIONS
  The combination of lenalidomide, low-dose dexamethasone, and rituximab achieved high response rates with durable responses in patients with rituximab-resistant, indolent B-cell and mantle cell lymphomas. Overall response rate increased from 29% after two 28-day cycles of lenalidomide and low-dose dexamethasone to 58% after the addition of rituximab, suggesting that lenalidomide can overcome resistance to rituximab.
authors.affiliation: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Tahamtan
authors.initials: T
authors.lastname: Ahmadi
authors.forename: Elise A
authors.initials: EA
authors.lastname: Chong
authors.forename: Amanda
authors.initials: A
authors.lastname: Gordon
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Aqui
authors.forename: Sunita D
authors.initials: SD
authors.lastname: Nasta
authors.forename: Jakub
authors.initials: J
authors.lastname: Svoboda
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Mato
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Schuster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000401:mortality; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: follicular lymphoma; immunomodulation; immunomodulatory therapy; lenalidomide; low-grade; lymphoma; non-Hodgkin lymphoma; rituximab