Originally published as JCO Early Release 10.1200/JCO.2008.17.1561 on March 2 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hochster, H. Articles by Horning, S. J. Search for Related Content PubMed PubMed Citation Articles by Hochster, H. Articles by Horning, S. J. Related Articles Related Editorial Social Bookmarking                            What's this?

Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study

From the New York University Medical Center, New York, NY; Dana Farber Cancer Institute, Statistical Center, Boston, MA; British Columbia Cancer Agency, Vancouver, Canada; Mayo Clinic, Rochester, MN; Northwestern University, Chicago, IL; Stanford University, Stanford, CA; and University of Maryland, Baltimore, MD.

Corresponding author: Howard S. Hochster, MD, New York University Cancer Institute, 160 East 34th St, New York, NY 10016; e-mail: howard.hochster{at}med.nyu.edu.

Purpose To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma.

Patients and Methods Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m² once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point.

Results Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 x 10^–10 [all patients]) and 64% MR v 33% OBS (HR = 0.4; P = 9.2 x 10^–8 [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03).

Conclusion The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS.

This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants No. CA21115, CA23318, CA66636, CA13650, and CA32291, and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Maintenance or Eradication of Residual Disease in Indolent Lymphoma: Where Do We Stand?
  Anton Hagenbeek
  JCO 2009 27: 1540-1542 [Full Text]

This article has been cited by other articles:

				F. Morschhauser, M. Dreyling, A. Rohatiner, F. Hagemeister, and A. Bischof Delaloye Rationale for Consolidation to Improve Progression-Free Survival in Patients with Non-Hodgkin's Lymphoma: A Review of the Evidence Oncologist, October 1, 2009; 14(suppl_2): 17 - 29. [Abstract] [Full Text] [PDF]

				O. Landgren, K. Dunleavy, and W. H. Wilson Re: Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized trials J Natl Cancer Inst, September 16, 2009; 101(18): 1287 - 1288. [Full Text] [PDF]

				L. Vidal, A. Gafter-Gvili, L. Leibovici, M. Dreyling, M. Ghielmini, and O. Shpilberg Response: Re: Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized trials J Natl Cancer Inst, September 16, 2009; 101(18): 1289 - 1290. [Full Text] [PDF]

				A. Hagenbeek Maintenance or Eradication of Residual Disease in Indolent Lymphoma: Where Do We Stand? J. Clin. Oncol., April 1, 2009; 27(10): 1540 - 1542. [Full Text] [PDF]