title: Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma.
abstract: BACKGROUND
  Mantle-cell lymphoma is generally incurable. Initial treatment is not standardized but usually includes cytotoxic chemotherapy. Lenalidomide, an immunomodulatory compound, and rituximab, an anti-CD20 antibody, are active in patients with recurrent mantle-cell lymphoma. We evaluated lenalidomide plus rituximab as a first-line therapy.
  
  
  METHODS
  We conducted a single-group, multicenter, phase 2 study with induction and maintenance phases. During the induction phase, lenalidomide was administered at a dose of 20 mg daily on days 1 through 21 of every 28-day cycle for 12 cycles; the dose was escalated to 25 mg daily after the first cycle if no dose-limiting adverse events occurred during the first cycle and was reduced to 15 mg daily during the maintenance phase. Rituximab was administered once weekly for the first 4 weeks and then once every other cycle until disease progression. The primary end point was the overall response rate. Secondary end points included outcomes related to safety, survival, and quality of life.
  
  
  RESULTS
  A total of 38 participants were enrolled at four centers from July 2011 through April 2014. The median age was 65 years. On the basis of the Mantle Cell Lymphoma International Prognostic Index scores, the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar (34%, 34%, and 32%, respectively). The most common grade 3 or 4 adverse events were neutropenia (in 50% of the patients), rash (in 29%), thrombocytopenia (in 13%), an inflammatory syndrome ("tumor flare") (in 11%), anemia (in 11%), serum sickness (in 8%), and fatigue (in 8%). At the median follow-up of 30 months (through February 2015), the overall response rate among the participants who could be evaluated was 92% (95% confidence interval [CI], 78 to 98), and the complete response rate was 64% (95% CI, 46 to 79); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be 85% (95% CI, 67 to 94), and the 2-year overall survival 97% (95% CI, 79 to 99). A response to treatment was associated with improvement in quality of life.
  
  
  CONCLUSIONS
  Combination biologic therapy consisting of lenalidomide plus rituximab was active as initial therapy for mantle-cell lymphoma. (Funded by Celgene and Weill Cornell Medical College; ClinicalTrials.gov number, NCT01472562.).
authors.affiliation: From the Meyer Cancer Center, Division of Hematology and Medical Oncology (J.R., P.M., R.R.F., A.R., J.L., O.K., M.C., J.P.L.), and Division of Biostatistics and Epidemiology (P.C.), Weill Cornell Medical College and New York-Presbyterian Hospital, New York; Moffitt Cancer Center, Tampa, FL (B.S.); University of Pennsylvania Abramson Cancer Center, Philadelphia (S.J.S., J.S.); and the University of Chicago Medical Center, Chicago (S.M.S.).
authors.forename: Jia
authors.initials: J
authors.lastname: Ruan
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.forename: Bijal
authors.initials: B
authors.lastname: Shah
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Schuster
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Amelyn
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Jakub
authors.initials: J
authors.lastname: Svoboda
authors.forename: Jessica
authors.initials: J
authors.lastname: Lewis
authors.forename: Orel
authors.initials: O
authors.lastname: Katz
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D057194:Intention to Treat Analysis; D000077269:Lenalidomide; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011788:Quality of Life; D000069283:Rituximab; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D013792:Thalidomide; D000077269:Lenalidomide