title: Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi.
abstract: OBJECTIVE
  To evaluate the efficacy of rituximab maintenance in 60- to 75-year-old patients with advanced follicular lymphoma responding to brief first-line chemoimmunotherapy followed by rituximab consolidation.
  
  
  METHODS
  A total of 234 treatment-naive 60- to 75-year-old patients began chemoimmunotherapy with four monthly courses of rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) followed by four weekly cycles of rituximab consolidation. Of these, 210 patients completed the planned treatment, and 202 responders were randomly assigned to rituximab maintenance (arm A) for 8 months, once every 2 months for a total of four doses, or to observation (arm B).
  
  
  RESULTS
  Median ages in arms A and B were 66 and 65 years, respectively. After induction and consolidation therapy, the overall response rate was 86%, with 69% complete remissions (CR). After a 42-month median follow-up from diagnosis, 3-year progression-free survival (PFS; the primary end point) and overall survival (OS) were 66% (95% CI, 59% to 72%) and 89% (95% CI, 85% to 93%), respectively. After randomization, 2-year PFS was 81% for rituximab maintenance versus 69% for observation, with a hazard ratio of 0.74 (95% CI, 0.45 to 1.21; P = .226), although this was not statistically significant. No differences between the two arms were detected for OS. Overall, the regimen was well-tolerated. The most frequent grade 3 to 4 toxicity was neutropenia (25% of treatment courses), with 13 infections. Two toxic deaths (0.8%) occurred during induction treatment.
  
  
  CONCLUSIONS
  A brief R-FND induction plus rituximab consolidation achieved excellent results with high CR and PFS rates, supporting the feasibility of this regimen in patients older than 60 years. A short rituximab maintenance did not achieve a statistically significant PFS improvement over observation.
authors: Umberto Vitolo, Marco Ladetto, Carola Boccomini, Barbara Botto, Annalisa Chiappella, Andrea Evangelista, Chiara Lobetti-Bodoni, and Giovannino Ciccone, Città della Salute e della Scienza Hospital and University, Turin; Luca Baldini, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore Policlinico, Università di Milano, Milan; Federico De Angelis, Sapienza University, Rome; Alessandra Tucci and Giuseppe Rossi, Spedali Civili Hospital and University, Brescia; Annalisa Chiarenza, Ferrarotto Hospital, Catania; Antonello Pinto, National Institute for Study and Cure of Tumors, Pascale Foundation; Amalia De Renzo, Federico II University, Napoli; Francesco Zaja, Santa Maria della Misericordia Hospital and University, Udine; Claudia Castellino, Santa Croce and Carle Hospital, Cuneo; Alessia Bari, University of Modena and Reggio Emilia, Modena; Isabel Alvarez De Celis, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia; Guido Parvis, San Luigi Gonzaga Hospital and University, Orbassano; and Enrica Gamba, Roche Italia, Monza, Italy.
authors: Umberto
authors: U
authors: Vitolo
authors: Marco
authors: M
authors: Ladetto
authors: Carola
authors: C
authors: Boccomini
authors: Luca
authors: L
authors: Baldini
authors: Federico
authors: F
authors: De Angelis
authors: Alessandra
authors: A
authors: Tucci
authors: Barbara
authors: B
authors: Botto
authors: Annalisa
authors: A
authors: Chiappella
authors: Annalisa
authors: A
authors: Chiarenza
authors: Antonello
authors: A
authors: Pinto
authors: Amalia
authors: A
authors: De Renzo
authors: Francesco
authors: F
authors: Zaja
authors: Claudia
authors: C
authors: Castellino
authors: Alessia
authors: A
authors: Bari
authors: Isabel
authors: I
authors: Alvarez De Celis
authors: Andrea
authors: A
authors: Evangelista
authors: Guido
authors: G
authors: Parvis
authors: Enrica
authors: E
authors: Gamba
authors: Chiara
authors: C
authors: Lobetti-Bodoni
authors: Giovannino
authors: G
authors: Ciccone
authors: Giuseppe
authors: G
authors: Rossi
mesh_terms: D000367:Age Factors; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060830:Consolidation Chemotherapy; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003907:Dexamethasone; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine