title: Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas.
abstract: OBJECTIVE
  Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cell-mediated cytotoxicity, has the potential to synergize with rituximab, an anti-CD20 mAb. We hypothesized that the addition of lenalidomide to rituximab would improve clinical outcomes in patients with B-cell lymphomas who were previously rituximab resistant, defined as no response to or progression of lymphoma within 6 months of rituximab-based therapy.
  
  
  METHODS
  We conducted a single-center, phase II trial in patients with indolent B-cell or mantle cell lymphomas who were previously rituximab resistant. Patients received 10 mg lenalidomide daily for 8 weeks, and then received four weekly doses of 375 mg/m(2) rituximab; lenalidomide continued during and after rituximab. Response to therapy was assessed after 8 weeks of lenalidomide and 12 weeks after first dose of rituximab. The primary endpoint was overall response rate (ORR) after lenalidomide and rituximab.
  
  
  RESULTS
  Fifty patients were enrolled and 43 patients completed both response assessments. ORR after 8 weeks of lenalidomide was 30.2%; 12 weeks after the addition of rituximab to lenalidomide, ORR increased to 62.8% (N = 43). For all patients (N = 50), median progression-free survival (PFS) is 22.2 months (median follow-up, 39.2 months). PFS after lenalidomide-rituximab was significantly longer than the PFS for the antecedent regimen used to define rituximab resistance (22.2 vs. 9.13 months, P = 0.0004).
  
  
  CONCLUSIONS
  This trial is the first to show that the combination of lenalidomide and rituximab overcomes prior rituximab resistance in patients with indolent B-cell and mantle cell lymphomas.
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Elise A
authors: EA
authors: Chong
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Tahamtan
authors: T
authors: Ahmadi
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Nicole A
authors: NA
authors: Aqui
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Jakub
authors: J
authors: Svoboda
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Sunita D
authors: SD
authors: Nasta
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Anthony R
authors: AR
authors: Mato
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Kristy M
authors: KM
authors: Walsh
authors: Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania. schustes@mail.med.upenn.edu.
authors: Stephen J
authors: SJ
authors: Schuster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D000077269:Lenalidomide; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017452:Receptors, IgG / Q000235:genetics; D019233:Retreatment; D000069283:Rituximab / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D000069283:Rituximab; D013792:Thalidomide; D000077269:Lenalidomide