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

J Clin Oncol. 2013 Sep 20;31(27):3351-9. doi: 10.1200/JCO.2012.44.8290. Epub 2013 Aug 19.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01144364.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Consolidation Chemotherapy
  • Dexamethasone / administration & dosage
  • Female
  • Humans
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / pathology
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Rituximab
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab
  • Dexamethasone
  • Mitoxantrone
  • Vidarabine
  • fludarabine

Associated data

  • ClinicalTrials.gov/NCT01144364