title: Treatment of older patients with mantle-cell lymphoma.
abstract: BACKGROUND
  The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission.
  
  
  METHODS
  We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression.
  
  
  RESULTS
  Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005).
  
  
  CONCLUSIONS
  R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).
authors.affiliation: Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.c.kluin@umcg.nl
authors.forename: H C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: E
authors.initials: E
authors.lastname: Hoster
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.forename: J
authors.initials: J
authors.lastname: Walewski
authors.forename: M
authors.initials: M
authors.lastname: Trneny
authors.forename: C H
authors.initials: CH
authors.lastname: Geisler
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: C
authors.initials: C
authors.lastname: Thieblemont
authors.forename: U
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: J K
authors.initials: JK
authors.lastname: Doorduijn
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
authors.forename: R
authors.initials: R
authors.lastname: Forstpointner
authors.forename: H
authors.initials: H
authors.lastname: Tilly
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: P
authors.initials: P
authors.lastname: Feugier
authors.forename: M
authors.initials: M
authors.lastname: Szymczyk
authors.forename: M
authors.initials: M
authors.lastname: Hallek
authors.forename: S
authors.initials: S
authors.lastname: Kremers
authors.forename: G
authors.initials: G
authors.lastname: Lepeu
authors.forename: L
authors.initials: L
authors.lastname: Sanhes
authors.forename: J M
authors.initials: JM
authors.lastname: Zijlstra
authors.forename: R
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: P J
authors.initials: PJ
authors.lastname: Lugtenburg
authors.forename: M
authors.initials: M
authors.lastname: Macro
authors.forename: M
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: V
authors.initials: V
authors.lastname: Procházka
authors.forename: F
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: V
authors.initials: V
authors.lastname: Ribrag
authors.forename: M
authors.initials: M
authors.lastname: Uppenkamp
authors.forename: M
authors.initials: M
authors.lastname: André
authors.forename: W
authors.initials: W
authors.lastname: Klapper
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: M
authors.initials: M
authors.lastname: Unterhalt
authors.forename: M H
authors.initials: MH
authors.lastname: Dreyling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D057194:Intention to Treat Analysis; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D011241:Prednisone