title: Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial.
abstract: BACKGROUND
  Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab plus chemotherapy regimen.
  
  
  METHODS
  The randomised, open-label PRIMA study was undertaken in 223 centres in 25 countries. 1217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-randomised immunochemotherapy induction regimens used in routine practice. 1019 patients achieving a complete or partial response were then randomly assigned to receive 2 years of rituximab maintenance therapy (375 mg/m(2) every 8 weeks) or observation. Treatment was assigned equally by centralised block randomisation, stratified by induction regimen, response, region, and centre. Neither the participants nor those giving the interventions, assessing outcomes, and analysing data were masked to group assignments. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00140582.
  
  
  RESULTS
  505 patients were assigned to rituximab maintenance and 513 to observation (one patient died during randomisation). With a median follow-up of 36 months (IQR 30-42), PFS was 74·9% (95% CI 70·9-78·9) in the rituximab maintenance group (130 patients progressed) and 57·6% (53·2-62·0) in the observation group (218 progressed; hazard ratio [HR] 0·55, 95% CI 0·44-0·68, p<0·0001). 2 years after randomisation, 361 patients (71·5%) in the rituximab maintenance group were in complete or unconfirmed complete response versus 268 (52·2%) in the observation group (p=0·0001). Overall survival did not differ significantly between groups (HR 0·87, 95% CI 0·51-1·47). Grade 3 and 4 adverse events were recorded in 121 patients (24%) in the rituximab maintenance group and 84 (17%) in the observation group (risk ratio 1·46, 95% CI 1·14-1·87; p=0·0026). Infections (grades 2-4) were the most common adverse event, occurring in 197 (39%) and 123 (24%) patients, respectively (risk ratio 1·62, 95% CI 1·35-1·96; p<0·0001).
  
  
  CONCLUSIONS
  2 years of rituximab maintenance therapy after immunochemotherapy as first-line treatment for follicular lymphoma significantly improves PFS.
  
  
  BACKGROUND
  Groupe d'Etude des Lymphomes de l'Adulte (GELA) and F Hoffmann-La Roche.
authors.affiliation: Hospices Civils de Lyon, Université Claude Bernard, UMR CNRS5239, Pierre-Bénite, France. gilles.salles@chu-lyon.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: John Francis
authors.initials: JF
authors.lastname: Seymour
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: David
authors.initials: D
authors.lastname: Belada
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
authors.forename: Réda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: John Vincent
authors.initials: JV
authors.lastname: Catalano
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.forename: Lars Moller
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Alain
authors.initials: A
authors.lastname: Delmer
authors.forename: David
authors.initials: D
authors.lastname: Simpson
authors.forename: Sirpa
authors.initials: S
authors.lastname: Leppa
authors.forename: Pierre
authors.initials: P
authors.lastname: Soubeyran
authors.forename: Anton
authors.initials: A
authors.lastname: Hagenbeek
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.forename: Tanin
authors.initials: T
authors.lastname: Intragumtornchai
authors.forename: Christophe
authors.initials: C
authors.lastname: Fermé
authors.forename: Maria Gomes
authors.initials: MG
authors.lastname: da Silva
authors.forename: Catherine
authors.initials: C
authors.lastname: Sebban
authors.forename: Andrew
authors.initials: A
authors.lastname: Lister
authors.forename: Jane A
authors.initials: JA
authors.lastname: Estell
authors.forename: Gustavo
authors.initials: G
authors.lastname: Milone
authors.forename: Anne
authors.initials: A
authors.lastname: Sonet
authors.forename: Myriam
authors.initials: M
authors.lastname: Mendila
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D000069283:Rituximab