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Improvement of Overall and Failure-Free Survival in Stage IV Follicular Lymphoma: 25 Years of Treatment Experience at The University of Texas M.D. Anderson Cancer Center

Qi Liu, Luis Fayad, Fernando Cabanillas, Fredrick B. Hagemeister, Gregory D. Ayers, Mark Hess, Jorge Romaguera, M. Alma Rodriguez, Apostolia M. Tsimberidou, Srdan Verstovsek, Anas Younes, Barbara Pro, Ming-Sheng Lee, Ana Ayala, Peter McLaughlin

From the Departments of Lymphoma/Myeloma, Biostatistics and Applied Mathematics, and Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.

Address reprint requests to Peter McLaughlin, MD, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 429, Houston, TX 77030; e-mail: pmclaugh{at}mdanderson.org

PURPOSE: Advanced-stage follicular lymphoma is considered incurable. The pace of improvements in treatment has been slow. This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002.

METHODS: Five consecutive studies (two were randomized trials) involving 580 patients were analyzed for overall survival (OS), failure-free survival (FFS), and survival after first relapse. A proportional hazards analysis, and subset analyses using the follicular lymphoma international prognostic index (FLIPI) score were performed. Treatment regimens included: cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin (CHOP-Bleo); CHOP-Bleo followed by interferon alfa (IFN-); a rotation of three regimens (alternating triple therapy), followed by IFN-; fludarabine, mitoxantrone, dexamethasone (FND) followed by IFN-; and FND plus delayed versus concurrent rituximab followed by IFN-.

RESULTS: Improvements in 5-year OS (from 64% to 95%) and FFS (from 29% to 60%) indicate steady progress, perhaps partly due to more effective salvage therapies, but the FFS data also indicate improved front-line therapies; these observations held true after controlling for differences in prognostic factors among the cohorts. The FLIPI model adds rigor to and facilitates comparisons among the different cohorts. An unexpected finding in this study was a trend toward an apparent FFS plateau.

CONCLUSION: Evolving therapy, including the incorporation of biologic agents, has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma. The apparent plateau in the FFS curve, starting approximately 8 to 10 years from the beginning of treatment, raises the issue of the potential curability of these patients.

Supported by National Cancer Institute Core Grant CA16672 awarded to The University of Texas M.D. Anderson Cancer Center, and Schering-Plough Corp, Integrated Therapeutics Group Inc, Genentech Inc, Biogen IDEC Pharmaceuticals, Berlex Corporation, Burroughs Wellcome Co.

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

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