Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia: an effective but myelosuppressive regimen to be offered to patients with advanced disease

Cancer. 2012 Jan 15;118(2):434-43. doi: 10.1002/cncr.26303. Epub 2011 Jul 5.


Background: The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced promising results in chronic lymphocytic leukemia and other lymphoproliferative disorders. The authors report the final results from a multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia (WM).

Methods: Forty-three patients with symptomatic WM that was untreated or pretreated with 1 line of chemotherapy received rituximab 375 mg/m(2) intravenously on day 1 and fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) intravenously on days 2 through 4. FCR was repeated every 28 days for up to 6 courses.

Results: The overall response rate was 79%, and the major response rate of 74.4%, including 11.6% complete remissions (CRs) and 20.9% very good partial remissions. An amelioration of the quality of responses was observed during follow-up, leading to 18.6% of CRs. No differences in terms of responses were observed among previously treated or untreated patients. Among the clinical and laboratory features that were considered, only the β2-microglobulin level had a significant impact in terms of achieving a major response. The major toxicity reported was grade 3/4 neutropenia, which occurred in 45% of courses and was the main reason for treatment discontinuation. After the end of treatment, 19 patients (44%) had long-lasting episodes of neutropenia. Three patients developed myelodysplastic syndrome during follow-up.

Conclusions: The FCR regimen was capable of neutralizing adverse prognostic factors and proved to be active in patients with WM, leading to rapid disease control and good-quality responses. Because myelosuppression was the main concern, further studies are warranted to optimize dosages and treatment duration.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunosuppression Therapy
  • Male
  • Middle Aged
  • Rituximab
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Waldenstrom Macroglobulinemia / drug therapy*


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