The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial

Haematologica. 2016 Feb;101(2):235-40. doi: 10.3324/haematol.2015.128710. Epub 2015 Nov 26.

Abstract

Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network.

Trial registration: ClinicalTrials.gov NCT00641095.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / therapeutic use*
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / mortality
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Second Primary / drug therapy*
  • Neoplasms, Second Primary / mortality
  • Neoplasms, Second Primary / pathology
  • Opportunistic Infections / drug therapy*
  • Opportunistic Infections / mortality
  • Opportunistic Infections / pathology
  • Rituximab / therapeutic use*
  • Survival Analysis
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use

Substances

  • Rituximab
  • Cyclophosphamide
  • Vidarabine
  • fludarabine

Associated data

  • ISRCTN/ISRCTN81133184
  • ClinicalTrials.gov/NCT00641095