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)

Cancer. 2010 Sep 15;116(18):4299-308. doi: 10.1002/cncr.25280.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lymphoma, Follicular / drug therapy*
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Neoplasms, Second Primary / epidemiology
  • Recurrence
  • Rituximab
  • Tumor Burden
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

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