title: Efficacy and safety of the combination of rituximab, fludarabine, and mitoxantrone for rituximab-naive, recurrent/refractory follicular non-Hodgkin lymphoma with high tumor burden: a multicenter phase 2 trial by the Groupe d'Etude des Lymphomes de l'Adulte (GELA) and Groupe Ouest Est des Leucémies et Autres Maladies du Sang (GOELAMS).
abstract: BACKGROUND
  This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone (R-FM) for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
  
  
  METHODS
  Fifty patients were enrolled who had received a maximum of 2 previous regimens, including 1 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/CHOP-like regimen but no previous exposure to rituximab, fludarabine, or mitoxantrone. At baseline, 58% of patients had bulky disease (lesion > 7 cm), 56% had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores (range, 3-5), and 22% were refractory. Treatment consisted of 4 courses of R-FM (rituximab 375 mg/m(2) intravenously on Day 1, fludarabine 25 mg/m(2) intravenously on Days 2 through 4, and mitoxantrone 10 mg/m(2) intravenously on Day 2, recycling at Day 28) and consolidation with 2 courses of fludarabine and mitoxantrone (the same regimen without rituximab).
  
  
  RESULTS
  The best response (84% overall response rate including 68% complete response/complete response unconfirmed) was achieved after 4 courses of R-FM. Response rates were high regardless of age, refractoriness to last previous therapy, and FLIPI score. After a median follow-up of 4 years, the 3-year progression-free survival rate was 47%, the event-free survival rate was 41%, and the 3-year overall survival rate was 66%. Grade ≥ 3 neutropenia and infections were the most common toxicities and occurred in 72% and 14% of patients, respectively.
  
  
  CONCLUSIONS
  Cytoreduction with 4 courses of R-FM was safe and highly efficient in patients with recurrent/refractory follicular lymphoma who had high tumor burden; however, better consolidation than FM is needed to further improve outcome.
authors.affiliation: Hematology Department, Lille University Hospital Center, Lille, France. franck-morschhauser@chru-lille.fr
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Catherine
authors.initials: C
authors.lastname: Sebban
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Phillippe
authors.initials: P
authors.lastname: Solal-Celigny
authors.forename: Herve
authors.initials: H
authors.lastname: Tilly
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
authors.forename: Christophe
authors.initials: C
authors.lastname: Fermé
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D012008:Recurrence; D000069283:Rituximab; D047368:Tumor Burden; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine