Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2009 Apr 1;27(10):1607-14.
doi: 10.1200/JCO.2008.17.1561. Epub 2009 Mar 2.

Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study

Howard Hochster  1 , Edie Weller, Randy D Gascoyne, Thomas M Habermann, Leo I Gordon, Theresa Ryan, Lijun Zhang, Natalia Colocci, Stanley Frankel, Sandra J Horning
Affiliations
Clinical Trial

Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study

Howard Hochster et al. J Clin Oncol. .

Abstract

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/m(2) 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.

PubMed Disclaimer

Conflict of interest statement

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

Figures

Fig 1.
Fig 1.
(A) Progression-free survival (PFS) for 311 evaluable indolent lymphoma patients randomly assigned to maintenance rituximab (MR; n = 158) or observation (OBS; n = 153). (B) PFS for 228 evaluable follicular lymphoma patients randomly assigned to MR (n = 115) or OBS (n = 113).
Fig 2.
Fig 2.
(A) Overall survival (OS) for 311 evaluable indolent lymphoma patients randomly assigned to maintenance rituximab (MR; n = 158) or observation (OBS; n = 153). (B) OS for 288 evaluable follicular lymphoma patients randomly assigned to MR (n = 115) or OBS (n = 113).
Fig 3.
Fig 3.
(A) Progression-free survival (PFS) for 158 evaluable maintenance rituximab (MR) patients according to minimal (n = 89) or gross (n = 69) residual disease after cyclophosphamide, vincristine, and prednisone (CVP) therapy. (B) PFS for 115 evaluable MR follicular lymphoma patients according to minimal (n = 67) or gross (n = 48) residual disease after CVP.
See this image and copyright information in PMC

Comment in

References

    1. Ezdinli EZ, Harrington DP, Kucuk O, et al. The effect of intensive intermittent maintenance therapy in advanced low-grade non-Hodgkin's lymphoma. Cancer. 1987;60:156–160. - PubMed
    1. Steward WP, Crowther D, McWilliam LJ, et al. Maintenance chlorambucil after CVP in the management of advanced stage, low-grade histologic type non-Hodgkin's lymphoma: A randomized prospective study with an assessment of prognostic factors. Cancer. 1988;61:441–447. - PubMed
    1. Hagenbeek A, Carde P, Meerwaldt JH, et al. Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol. 1998;16:41–47. - PubMed
    1. Hiddemann W, Griesinger F, Unterhalt M. Interferon alfa for the treatment of follicular lymphomas. Cancer J Sci Am. 1998;4(suppl 2):S13–S18. - PubMed
    1. Rohatiner A, Radford J, Deakin D, et al. A randomized controlled trial to evaluate the role of interferon as initial and maintenance therapy in patients with follicular lymphoma. Br J Cancer. 2001;85:29–35. - PMC - PubMed

Publication types