Recombinant interferon-α2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: Final analysis of CALGB 8691

S. M. Smith, J. Johnson, B. D. Cheson, G. Canellos, G. Petroni, M. Oken, D. Duggan, D. Hurd, J. P. Gockerman, B. Parker, J. Prchal, B. A. Peterson

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6 Scopus citations


Recombinant interferon alpha-2b (IFN-α2) has direct and indirect antiproliferative effects in lymphoma, and may augment cytotoxicity when combined with chemotherapy. CALGB 8691 is a randomized study of daily oral cyclophosphamide (CPA) at 100 mg/m2 with or without IFN-α2 at 2 × 106 IU/m2 three times per week, followed by a second randomization between IFN-α2 maintenance (2 × 106 IUm2 three times weekly) versus observation in treatment-nave patients with follicular lymphoma FL. Five hundred eighty-one patients were randomized to either CPA (n = 293) or CPA plus IFN-α2 (n = 288). One hundred five responding patients were randomized to observation and 99 to maintenance IFN-α2. With a median follow-up of 11.5 years, the median event-free and overall survival (OS) for CPA induction alone were 2.5 years (95% CI 2.2, 3.0) and 9 years (95% CI 7.7, 10.2), compared to 2.4 years (95% CI 2.1, 3.1) and 8.4 years (95% CI 7.5, 11.1) for the combination arm (p = NS). Patients with a partial response (PR) and randomized to observation had the worst outcome (event-free survival (EFS) 1.8 years versus 3.9 years; p = 0.002). Patients with a PR randomized to IFN-α2 had a similar EFS to compared to patients with complete response CR, but this did not translate into a survival advantage. Myelosuppression was increased in IFN-α2-containing arms. Despite the small benefit in EFS in patients with PR randomized to IFN-α2 maintenance, we conclude that the addition of low dose IFN-α2 did not significantly improve the response rate, duration of response, event-free, or OS obtained with single-agent daily oral CPA in patients with previously untreated FL.

Original languageEnglish (US)
Pages (from-to)1606-1617
Number of pages12
JournalLeukemia and Lymphoma
Issue number10
StatePublished - 2009

Bibliographical note

Funding Information:
The research for CALGB 8691 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. S. M. smith is supported by grant CA41287; J. Johnson and G. Petroni by CA33601; B. D. Cheson by CA77597; G. Canellos by CA32291; M. Oken by CA21115; D. Duggan by CA21060; D. Hurd by CA03927; P. Gockerman by CA 47577; B. Parker by CA11789, and B. A. Peterson by CA16450. The following institutions participated in this study: Columbia University, New York, NY; Dana-Farber Cancer Institute, Boston, MA – Eric P. Winer, M.D., supported by CA32291; Dartmouth Medical School – Norris Cotton Cancer Center, Lebanon, NH – Marc S. Ernstoff, M.D., supported by CA04326; Duke University Medical Center, Durham, NC – Jeffrey Crawford, M.D., supported by CA47577; Finsen Institute, Copenhagen, DK; Long Island Jewish Medical Center, Lake Success, NY – Kanti R. Rai, M.D., supported by CA11028; Massachusetts General Hospital, Boston, MA – Jeffrey W. Clark, M.D., supported by CA12449; McGill University, Montreal, QC – Gerald Batist, M.D.; Mount Sinai School of Medicine, New York, NY – Lewis R. Silverman, M.D., supported by CA04457; Rhode Island Hospital, Providence, RI – William Sikov, M.D., supported by CA08025; Roswell Park Cancer Institute, Buffalo, NY – Ellis Levine, M.D., supported by CA02599; State University of New York Upstate Medical University, Syracuse, NY – Stephen L. Graziano, M.D., supported by CA21060; Suny-Maimonides Medical Center, Brooklyn, NY; University of Alabama Birmingham, Birmingham, AL – Robert Diasio, M.D., supported by CA47545; University of California at San Diego, San Diego, CA – Barbara A. Parker, M.D., supported by CA11789; University of Chicago, Chicago, IL – Gini Fleming, M.D., supported by CA41287; University of Iowa, Iowa City, IA – Daniel A. Vaena, M.D., supported by CA47642; University of Maryland Greenebaum Cancer Center, Baltimore, MD – Martin Edelman, M.D., supported by CA31983; University of Massachusetts Medical School, Worcester, MA – William V. Walsh, M.D., supported by CA37135; University of Minnesota, Minneapolis, MN – Bruce A Peterson, M.D., supported by CA16450; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO – Michael C Perry, M.D., supported by CA12046; University of North Carolina at Chapel Hill, Chapel Hill, NC – Thomas C. Shea, M.D., supported by CA47559; University of Tennessee Memphis, Memphis, TN – Harvey B. Niell, M.D., supported by CA47555; Wake Forest University School of Medicine, Winston-Salem, NC – David D Hurd, M.D., supported by CA03927; Walter Reed Army Medical Center, Washington, DC – Thomas Reid, M.D., supported by CA26806; Washington University School of Medicine, St. Louis, MO – Nancy Bartlett, M.D., supported by CA77440; Weill Medical College of Cornell University, New York, NY – John Leonard, M.D., supported by CA07968; Eastern Cooperative Oncology Group, Philadelphia, PA – Robert L. Comis, M.D., Chairman; supported by CA21115.


  • Cyclophosphamide
  • Follicular lymphoma
  • Interferon
  • Maintenance

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