title: 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.
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.
authors.affiliation: Derriford Hospital, Plymouth, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Rule
authors.affiliation: Cancer Reasearch UK and UCL Cancer Trials Centre, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.affiliation: University of Southampton, Southampton, UK.
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Johnson
authors.affiliation: Musgrove Park Hospital, Taunton, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Bolam
authors.affiliation: Addenbrookes Hospital, Cambridge, UK.
authors.forename: George
authors.initials: G
authors.lastname: Follows
authors.affiliation: Cancer Reasearch UK and UCL Cancer Trials Centre, London, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Gambell
authors.affiliation: St. James's University Hospital, Leeds, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.affiliation: HMDS, Leeds General Infirmary, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jack
authors.affiliation: Musgrove Park Hospital, Taunton, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Cancer Reasearch UK and UCL Cancer Trials Centre, London, UK.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Kirkwood
authors.affiliation: Royal Cornwall Hospital, Truro, UK.
authors.forename: Anton
authors.initials: A
authors.lastname: Kruger
authors.affiliation: Kent and Canterbury Hospital, Canterbury, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pocock
authors.affiliation: The Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Cancer Reasearch UK and UCL Cancer Trials Centre, London, UK.
authors.forename: Milena
authors.initials: M
authors.lastname: Toncheva
authors.affiliation: Maria Sklodowska-Curie Institute and Oncology Centre, Gilwice, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.affiliation: UCL Cancer Institute, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Linch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009894:Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069283:Rituximab / Q000627:therapeutic use*; D016019:Survival Analysis; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine