title: Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study.
abstract: OBJECTIVE
  In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the maintenance phase was 33 months. Now, we report the long-term outcome of maintenance treatment, with a median follow-up of 6 years.
  
  
  METHODS
  Overall, 465 patients were randomly assigned to induction with either six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab plus CHOP (R-CHOP). Those in complete remission or partial remission after induction (n = 334) were randomly assigned to maintenance treatment with rituximab (375 mg/m(2) intravenously once every 3 months) or observation.
  
  
  RESULTS
  Rituximab maintenance significantly improved progression-free survival (PFS) compared with observation (median, 3.7 years v 1.3 years; P < .001; hazard ratio [HR], 0.55), both after CHOP induction (P < .001; HR, 0.37) and R-CHOP (P = .003; HR, 0.69). The 5-year overall survival (OS) was 74% in the rituximab maintenance arm, and it was 64% in the observation arm (P = .07). After progression, a rituximab-containing salvage therapy was given to 59% of patients treated with CHOP followed by observation, compared with 26% after R-CHOP followed by rituximab maintenance. Rituximab maintenance was associated with a significant increase in grades 3 to 4 infections: 9.7% v 2.4% (P = .01).
  
  
  CONCLUSIONS
  With long-term follow-up, we confirm the superior PFS with rituximab maintenance in relapsed/resistant FL. The improvement of OS did not reach statistical significance, possibly because of the unbalanced use of rituximab in post-protocol salvage treatment.
authors.affiliation: Department of Hematology, F4-224, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. M.H.vanOers@AMC.UVA.NL
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Martine
authors.initials: M
authors.lastname: Van Glabbeke
authors.forename: Livia
authors.initials: L
authors.lastname: Giurgea
authors.forename: Richard
authors.initials: R
authors.lastname: Klasa
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marcus
authors.forename: Max
authors.initials: M
authors.lastname: Wolf
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Mars
authors.initials: M
authors.lastname: van t Veer
authors.forename: Andrej
authors.initials: A
authors.lastname: Vranovsky
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Anton
authors.initials: A
authors.lastname: Hagenbeek
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D012074:Remission Induction; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone