Originally published as JCO Early Release 10.1200/JCO.2005.05.1003 on June 5 2006

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Rituximab-CHOP Versus CHOP Alone or With Maintenance Rituximab in Older Patients With Diffuse Large B-Cell Lymphoma

Thomas M. Habermann, Edie A. Weller, Vicki A. Morrison, Randy D. Gascoyne, Peter A. Cassileth, Jeffrey B. Cohn, Shaker R. Dakhil, Bruce Woda, Richard I. Fisher, Bruce A. Peterson, Sandra J. Horning

From the Mayo Clinic, Rochester; Veterans’ Administration Medical Center, University of Minnesota, Minneapolis, MN; Dana-Farber Cancer Institute Statistical Center, Boston; University of Massachusetts Medical School, Worcester, MA; University of Miami, Miami, FL; Albert Einstein Cancer Center, Philadelphia, PA; Wichita Community Clinical Oncology Program, Wichita, KS; University of Rochester, Rochester, NY; Stanford University, Stanford, CA; and British Columbia Cancer Agency, Vancouver, British Columbia, Canada

Address reprint requests to Thomas M. Habermann, MD, Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: habermann.thomas{at}mayo.edu

PURPOSE: To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients.

PATIENTS AND METHODS: Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided.

RESULTS: Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone.

CONCLUSION: Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.

Supported in part by Public Health Service Grants No. CA13650, CA23318, CA66636, CA21115, CA16450, CA35431, CA11083, and CA32291 and by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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

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