Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial

Ann Hematol. 2017 Apr;96(4):639-646. doi: 10.1007/s00277-017-2920-2. Epub 2017 Jan 18.


Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Keywords: FCM regimen; Follicular lymphoma; Outcome; Safety; Secondary neoplasia.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphoma, Follicular / diagnosis
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / mortality
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage*
  • Mitoxantrone / adverse effects
  • Survival Rate / trends
  • Time Factors
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*


  • Cyclophosphamide
  • Mitoxantrone
  • Vidarabine
  • fludarabine